Diagenode

Bioruptor

2125 publications found.

MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1
Published: July, 2017

Abstract: Pre–B-cell leukemia homeobox (PBX) and myeloid ecotropic viral integration site (MEIS) proteins control cell fate decisions in many physiological and pathophysiological contexts, but how these proteins function mechanistically remains poorly...
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Genomic Characterization of Murine Monocytes Reveals C/EBPβ Transcription Factor Dependence of Ly6C- Cells
Published: May, 2017

Abstract: Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. MurineLy6C+ monocytes display developmental plasticity and are recruited to complement tissue-resident macrophages and dendritic...
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The adaptor protein ARA55 and the nuclear kinase HIPK1 assist c-Myb in recruiting p300 to chromatin
Published: May, 2017

Abstract: LIM-domain proteins, containing multiple cysteine-rich zinc finger-like motifs, have been shown to play diverse roles in several cellular processes. A common theme is that they mediate important protein-protein interactions that are key to their f...
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Novel Molecular Mechanism of Regulation of CD40 Ligand by the Transcription Factor GLI2
Published: April, 2017

Abstract: The interaction between tumor cells and their surrounding microenvironment is essential for the growth and persistence of cancer cells. This interaction is mediated, in part, by cytokines. Although the role of cytokines in normal and malignant cel...
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Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis
Published: April, 2017

Abstract: OBJECTIVE: Aberrant activation of synovial fibroblasts (SFs) is a key determinant in the pathogenesis of rheumatoid arthritis (RA). We aimed to produce a map of gene expression and epigenetic changes occurring in this cell type during disease pro...
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The Rhomboid Protease GlpG Promotes the Persistence of Extraintestinal Pathogenic Escherichia coli within the Gut
Published: April, 2017

Abstract: Extraintestinal pathogenic Escherichia coli (ExPEC) strains are typically benign within the  mammalian gut, but can disperse to extraintestinal sites to cause disease. As occupation of the  intestinal tract is often a prerequisite for Ex...
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The antiproliferative ELF2 isoform, ELF2B, induces apoptosis in vitro and perturbs early lymphocytic development in vivo
Published: March, 2017

Abstract: Background ELF2 (E74-like factor 2) also known as NERF (new Ets-related factor), a member of the Ets family of transcription factors, regulates genes important in B and T cell development, cell cycle progression, and angiogenesis. Conserved ELF...
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Islet-1 induces the differentiation of mesenchymal stem cells into cardiomyocyte-like cells through the regulation of Gcn5 and DNMT-1
Published: March, 2017

Abstract: Previous studies from this group demonstrated that insulin gene enhancer binding protein ISL-1 (Islet-1) specifically induces the differentiation of mesenchymal stem cells (MSCs) into cardiomyocyte‑like cells through histone acetylation. However, ...
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Differentiation of Mouse Enteric Nervous System Progenitor Cells is Controlled by Endothelin 3 and Requires Regulation of Ednrb by SOX10 and ZEB2
Published: January, 2017

Abstract: Background & Aims Maintenance and differentiation of progenitor cells in the developing enteric nervous system (ENS) are controlled by molecules such as the signaling protein endothelin 3 (EDN3), its receptor (the endothelin receptor type B...
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m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition
Published: December, 2016

Abstract: The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one...
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Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression
Published: December, 2016

Abstract: ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress respon...
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Stem cell-like transcriptional reprogramming mediates metastatic
Published: December, 2016

Abstract: Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here...
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Evaluating the Feasibility of DNA Methylation Analyses Using Long-Term Archived Brain Formalin-Fixed Paraffin-Embedded Samples
Published: December, 2016

Abstract: We here characterize the usability of archival formalin-fixed paraffin-embedded (FFPE) brain tissue as a resource for genetic and DNA methylation analyses with potential relevance for brain-manifested diseases. We analyzed FFPE samples from The Br...
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Nitric oxide modulates histone acetylation at stress genes by inhibition of histone deacetylases
Published: December, 2016

Abstract: Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by ...
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Alu repeats as transcriptional regulatory platforms in macrophage responses to M. tuberculosis infection
Published: December, 2016

Abstract: To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo...
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Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs
Published: December, 2016

Abstract: The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. W...
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TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells
Published: November, 2016

Abstract: BACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable ele...
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β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance
Published: November, 2016

Abstract: Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic ap...
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EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells
Published: November, 2016

Abstract: The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these...
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Genome-wide DNA promoter methylation and transcriptome analysis in human adipose tissue unravels novel candidate genes for obesity
Published: November, 2016

Abstract: Objective/methods DNA methylation plays an important role in obesity and related metabolic complications. We examined genome-wide DNA promoter methylation along with mRNA profiles in paired samples of human subcutaneous adipose tissue (SAT) and o...
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The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs
Published: November, 2016

Abstract: The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found ...
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A set of novel automated quantitative microproteomics protocols for small sample amounts and its application to kidney tissue substructures
Published: November, 2016

Abstract: Here we assessed the ability of an automated sample preparation device equipped with disposable microcolumns to prepare mass-limited samples for high-sensitivity quantitative proteomics, using both label-free and isobaric labeling approaches. Firs...
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Transcriptional Activation of Pericentromeric Satellite Repeats and Disruption of Centromeric Clustering upon Proteasome Inhibition
Published: November, 2016

Abstract: Heterochromatinisation of pericentromeres, which in mice consist of arrays of major satellite repeats, are important for centromere formation and maintenance of genome stability. The dysregulation of this process has been linked to genomic stress ...
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Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks
Published: October, 2016

Abstract: As chromatin immunoprecipitation (ChIP) sequencing is becoming the dominant technique for studying chromatin modifications, new protocols surface to improve the method. Bioinformatics is also essential to analyze and understand the results, and pr...
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Genetic variation at the 8q24.21 renal cancer susceptibility locus affects HIF binding to a MYC enhancer
Published: October, 2016

Abstract: Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have a...
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DNA fragmentation and quality control analysis
Published: September, 2016

Abstract: Optimal data generation using NGS platforms relies on a few sample-preparation prerequisites, namely, precise DNA fragmentation, size-range analysis, and smear quantification. The Diagenode One, Bioruptor®, Megaruptor®, and Fragment A...
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Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing
Published: September, 2016

Abstract: Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed g...
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Converging disease genes in ICF syndrome: ZBTB24 controls expression of CDCA7 in mammals
Published: July, 2016

Abstract: For genetically heterogeneous diseases a better understanding of how the underlying gene defects are functionally interconnected will be important for dissecting disease etiology. The Immunodeficiency, Centromeric instability, Facial anomalies (IC...
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Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots
Published: July, 2016

Abstract: Background In utero and early-life experienced environmental exposures are suggested to play an important role in many multifactorial diseases potentially mediated through lasting effects on the epigenome. As the epigenome in addition remains modi...
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UMI-4C for quantitative and targeted chromosomal contact profiling
Published: July, 2016

Abstract: We developed a targeted chromosome conformation capture (4C) approach that uses unique molecular identifiers (umis) to derive high-complexity quantitative chromosome contact profiles with controlled signal-to-noise ratios. UMI-4C detects chromosom...
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The dynamic interactome and genomic targets of Polycomb complexes during stem-cell differentiation
Published: July, 2016

Abstract: Although the core subunits of Polycomb group (PcG) complexes are well characterized, little is known about the dynamics of these protein complexes during cellular differentiation. We used quantitative interaction proteomics and genome-wide profili...
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Osterix and RUNX2 are Transcriptional Regulators of Sclerostin in Human Bone
Published: May, 2016

Abstract: Sclerostin, encoded by the SOST gene, works as an inhibitor of the Wnt pathway and therefore is an important regulator of bone homeostasis. Due to its potent action as an inhibitor of bone formation, blocking sclerostin activity is the purpose of ...
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Characterization of novel Bovine Leukemia Virus (BLV) antisense transcripts by deep sequencing reveals constitutive expression in tumors and transcriptional interaction with viral microRNAs
Published: May, 2016

Abstract: Background Bovine Leukemia Virus (BLV) is a deltaretrovirus closely related to the Human T cell leukemia virus-1 (HTLV-1). Cattle are the natural host of BLV where it integrates into B-cells, producing a lifelong infection. Most infected animals ...
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Mutations in GAS8, A Gene Encoding A Nexin-Dynein Regulatory Complex Subunit, Cause Primary Ciliary Dyskinesia With Axonemal Disorganization
Published: April, 2016

Abstract: Primary ciliary dyskinesia (PCD) is an autosomal recessive disease characterized by chronic respiratory infections of the upper and lower airways, hypofertility, and, in approximately half of the cases, situs inversus. This complex phenotype resul...
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Histamine 1 receptor-Gβγ-cAMP/PKA-CFTR pathway mediates the histamine-induced resetting of the suprachiasmatic circadian clock
Published: March, 2016

Abstract: Background Recent evidence indicates that histamine, acting on histamine 1 receptor (H1R), resets the circadian clock in the mouse suprachiasmatic nucleus (SCN) by increasing intracellular Ca2+ concentration ([Ca2+]i) through the activation of Ca...
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saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription
Published: February, 2016

Abstract: Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigen...
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Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.
Published: February, 2016

Abstract: Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive ...
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ARTD1 regulates osteoclastogenesis and bone homeostasis by dampening NF-κB-dependent transcription of IL-1β
Published: February, 2016

Abstract: While ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) and its enzymatic activity have been shown to be important for reprogramming and differentiation of cells, such as during adipogenesis, their role and mechanism in regula...
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RecG Directs DNA Synthesis during Double-Strand Break Repair
Published: February, 2016

Abstract: Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and r...
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The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis
Published: February, 2016

Abstract: The association between impaired fetal growth and postnatal development of obesity has been demonstrated before. By comparing adipocytes differentiated from Mesenchymal Stem Cells (MSCs) taken from the umbilical cord and derived from normal and gr...
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Desensitization and incomplete recovery of hepatic target genes after chronic thyroid hormone treatment and withdrawal in male adult mice
Published: February, 2016

Abstract: Here, we examined changes in hepatic gene expression and serum TH/thyrotropin (TSH) levels in adult male mice treated either with a single T3 (20 g/100 g body weight) injection (acute T3) or daily injections for 14 days (chronic T3) followed ...
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Rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) for analysis of chromatin complexes
Published: January, 2016

Abstract: Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) is a method that allows the study of protein complexes, in particular chromatin and transcription factor complexes, in a rapid and robust manner by mass spectrometry (MS). Th...
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Chromatin Immunoprecipitation Assay for the Identification of Arabidopsis Protein-DNA Interactions In Vivo
Published: January, 2016

Abstract: Intricate gene regulatory networks orchestrate biological processes and developmental transitions in plants. Selective transcriptional activation and silencing of genes mediate the response of plants to environmental signals and developmental cues...
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Analysis of EZH2: micro-RNA network in low and high grade astrocytic tumors
Published: January, 2016

Abstract: Enhancer of Zeste homologue2 (EZH2) is an epigenetic regulator that functions as oncogene in astrocytic tumors, however, EZH2 regulation remains little studied. In this study, we measured EZH2 levels in low (Gr-II,DA) and high grade (Gr-IV,GBM) as...
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Transducin-like enhancer of split-1 is expressed and functional in human macrophages
Published: December, 2015

Abstract: Macrophages display heterogeneous phenotypes, including the classical M1 proinflammatory and the alternative M2 anti-inflammatory polarization states. The transducin-like enhancer of split-1 (TLE1) is a transcriptional corepressor whose functions ...
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Epigenome-wide effects of vitamin D and their impact on the transcriptome of human monocytes involve CTCF
Published: December, 2015

Abstract: The physiological functions of vitamin D are mediated by its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) activating the transcription factor vitamin D receptor (VDR). The chromatin-organizing protein CTCF bound to 14% of the 1,25(OH)2...
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Standardizing chromatin research: a simple and universal method for ChIP-seq
Published: December, 2015

Abstract: Here we demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction b...
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HNF1β drives glutathione (GSH) synthesis underlying intrinsic carboplatin resistance of ovarian clear cell carcinoma (OCCC)
Published: October, 2015

Abstract: Chemoresistance to platinum-based antineoplastic agents is a consistent feature among ovarian carcinomas; however, whereas high-grade serous carcinoma (OSC) acquires resistance during chemotherapy, ovarian clear cell carcinoma (OCCC) is intrinsica...
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NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program
Published: October, 2015

Abstract: Abstract Cell fate specification relies on the action of critical transcription factors that become available at distinct stages of embryonic development. One such factor is NeuroD1, which is essential for eliciting the neuronal development progr...
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Acetylations of Ftz-F1 and histone H4K5 are required for the fine-tuning of ecdysone biosynthesis during Drosophila metamorphosis.
Published: August, 2015

Abstract: The molting during Drosophila development is tightly regulated by the ecdysone hormone. Several steps of the ecdysone biosynthesis have been already identified but the regulation of the entire process has not been clarified yet. We have previously...
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Acetylation of intragenic histones on HPV16 correlates with enhanced HPV16 gene expression.
Published: August, 2015

Abstract: We report that many histone modifications are unevenly distributed over the HPV16 genome in cervical cancer cells as well as in HPV16-immortalized keratinocytes. For example, H3K36me3 and H3K9Ac that are common in highly expressed cellular genes a...
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Folic acid administration inhibits amyloid β-peptide accumulation in APP/PS1 transgenic mice.
Published: August, 2015

Abstract: Alzheimer's disease (AD) is associated with malnutrition, altered one-carbon metabolism and increased hippocampal amyloid-β peptide (Aβ) accumulation. Aberrant DNA methylation may be an epigenetic mechanism that underlies AD pathogenesis...
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Enhancer of zeste homolog-2 (EZH2) methyltransferase regulates transgelin/smooth muscle-22α expression in endothelial cells in response to interleukin-1β and transforming growth factor-β2.
Published: August, 2015

Abstract: Smooth muscle-22α (SM22α), encoded by transgelin (TAGLN), is expressed in mesenchymal lineage cells, including myofibroblasts and smooth muscle cells. It is an F-actin binding protein that regulates the organization of actin cytoskelet...
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The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters.
Published: August, 2015

Abstract: UNLABELLED: The human interferon-inducible IFI16 protein, an innate immune sensor of intracellular DNA, was recently demonstrated to act as a restriction factor for human cytomegalovirus (HCMV) and herpes simplex virus 1 (HSV-1) infection by inhib...
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Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Published: July, 2015

Abstract: Sox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cance...
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Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer.
Published: July, 2015

Abstract: Altered epigenetic mechanisms, similar to gene mutations, contribute to the pathogenesis and molecular heterogeneity of neoplasms, including colorectal cancer (CRC). Enhancer of zeste 2 (EZH2) is a histone methyltransferase, which is involved in e...
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GCDCA down-regulates gene expression by increasing Sp1 binding to the NOS-3 promoter in an oxidative stress dependent manner.
Published: July, 2015

Abstract: During the course of cholestatic liver diseases, the toxic effect of bile acids accumulation has been related to the decreased expression of endothelial nitric oxide synthase (NOS-3) and cellular oxidative stress increase. In the present study, we...
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Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells
Published: June, 2015

Abstract: Transposable elements comprise roughly 40% of mammalian genomes. They have an active role in genetic variation, adaptation and evolution through the duplication or deletion of genes or their regulatory elements, and transposable elements themselve...
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Lysine-specific demethylase (LSD1/KDM1A) and MYCN cooperatively repress tumor suppressor genes in neuroblastoma.
Published: June, 2015

Abstract: The chromatin-modifying enzyme lysine-specific demethylase 1, KDM1A/LSD1 is involved in maintaining the undifferentiated, malignant phenotype of neuroblastoma cells and its overexpression correlated with aggressive disease, poor differentiation an...
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Concurrent whole-genome haplotyping and copy-number profiling of single cells.
Published: June, 2015

Abstract: Methods for haplotyping and DNA copy-number typing of single cells are paramount for studying genomic heterogeneity and enabling genetic diagnosis. Before analyzing the DNA of a single cell by microarray or next-generation sequencing, a whole-geno...
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Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma.
Published: June, 2015

Abstract: Pathologic c-Myc expression is frequently detected in human cancers, including Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by binding to acet...
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Gene chip analysis of Arabidopsis thaliana genomic DNA methylation and gene expression in response to carbendazim.
Published: June, 2015

Abstract: OBJECTIVES: To examine the effects of carbendazim on Arabidopsis genomic DNA methylation and gene expression. RESULTS: Carbendazim caused widespread changes in gene loci methylation and gene expression. With 0.1 mM (D2) and 0.2 mM (D3) carbendazim...
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Yap7 is a transcriptional repressor of nitric oxide oxidase in yeasts, which arose from neofunctionalization after whole genome duplication.
Published: June, 2015

Abstract: Flavohemoglobins are the main detoxifiers of nitric oxide (NO) in bacteria and fungi and are induced in response to nitrosative stress. In fungi, the flavohemoglobin encoding gene YHB1 is positively regulated by transcription factors which are act...
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Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer.
Published: June, 2015

Abstract: Prostate cancer (PCa) progression is regulated by the androgen receptor (AR); however, patients undergoing androgen-deprivation therapy (ADT) for disseminated PCa eventually develop castration-resistant PCa (CRPC). Results of previous studies indi...
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Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.
Published: June, 2015

Abstract: The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has a...
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A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.
Published: June, 2015

Abstract: Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promot...
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Th2 Cytokines Augment IL-31/IL-31RA Interactions via STAT6-dependent IL-31RA Expression.
Published: May, 2015

Abstract: Interleukin 31 receptor α (IL-31RA) is a novel Type I cytokine receptor that pairs with oncostatin M receptor to mediate IL-31 signaling. Binding of IL-31 to its receptor results in the phosphorylation and activation of STATs, MAPK, and JNK signal...
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The N-terminal Set-β Protein Isoform Induces Neuronal Death.
Published: May, 2015

Abstract: Set-β protein plays different roles in neurons, but the diversity of Set-β neuronal isoforms and their functions have not been characterized. The expression and subcellular localization of Set-β are altered in Alzheimer disease, cleavage of Set-β ...
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Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.
Published: May, 2015

Abstract: An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimul...
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Glucocorticoid receptor and Klf4 co-regulate anti-inflammatory genes in keratinocytes.
Published: May, 2015

Abstract: The glucocorticoid (GC) receptor (GR) and Kruppel-like factor Klf4 are transcription factors that play major roles in skin homeostasis. However, whether these transcription factors cooperate in binding genomic regulatory regions in epidermal kerat...
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Involvement of RNA Polymerase III in Immune Responses.
Published: May, 2015

Abstract: Inflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metas...
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Control of brain patterning by Engrailed paracrine transfer: a new function of the Pbx interaction domain.
Published: May, 2015

Abstract: Homeoproteins of the Engrailed family are involved in the patterning of mesencephalic boundaries through a mechanism classically ascribed to their transcriptional functions. In light of recent reports on the paracrine activity of homeoproteins, in...
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The Novel Gene CRNDE Encodes a Nuclear Peptide (CRNDEP) Which Is Overexpressed in Highly Proliferating Tissues.
Published: May, 2015

Abstract: CRNDE, recently described as the lncRNA-coding gene, is overexpressed at RNA level in human malignancies. Its role in gametogenesis, cellular differentiation and pluripotency has been suggested as well. Herein, we aimed to verify our hypothesis th...
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Aerobic glycolysis tunes YAP/TAZ transcriptional activity.
Published: May, 2015

Abstract: Increased glucose metabolism and reprogramming toward aerobic glycolysis are a hallmark of cancer cells, meeting their metabolic needs for sustained cell proliferation. Metabolic reprogramming is usually considered as a downstream consequence of t...
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Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium
Published: May, 2015

Abstract: Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote a...
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Antisense RNA Controls LRP1 Sense Transcript Expression through Interaction with a Chromatin-Associated Protein, HMGB2.
Published: May, 2015

Abstract: Long non-coding RNAs (lncRNAs), including natural antisense transcripts (NATs), are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of...
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Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction.
Published: May, 2015

Abstract: INTRODUCTION: The Tie2/angiopoietin (Tie2/Ang) and vascular endothelial growth factor receptor-ligand systems (VEGFR/VEGF) are recognized to play important roles in the regulation of microvascular endothelial function. Downregulation of these gen...
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Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance.
Published: May, 2015

Abstract: FOXM1 has been implicated in taxane resistance, but the molecular mechanism involved remains elusive. In here, we show that FOXM1 depletion can sensitize breast cancer cells and mouse embryonic fibroblasts into entering paclitaxel-induced senescen...
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TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis.
Published: May, 2015

Abstract: Tumor cells frequently disseminate through the lymphatic system during metastatic spread of breast cancer and many other types of cancer. Yet it is not clear how tumor cells make their way into the lymphatic system and how they choose between lymp...
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Characterization of genome-wide ordered sequence-tagged Mycobacterium mutant libraries by Cartesian Pooling-Coordinate Sequencing.
Published: May, 2015

Abstract: Reverse genetics research approaches require the availability of methods to rapidly generate specific mutants. Alternatively, where these methods are lacking, the construction of pre-characterized libraries of mutants can be extremely valuable. Ho...
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Roles of hepatic glucokinase in intertissue metabolic communication: Examination of novel liver-specific glucokinase knockout mice.
Published: May, 2015

Abstract: Glucokinase is expressed principally in pancreatic β-cells and hepatocytes, and catalyzes the phosphorylation of glucose to glucose-6-phosphate, a rate-limiting step of glycolysis. To better understand the roles of hepatic glucokinase, we generate...
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Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.
Published: May, 2015

Abstract: CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for t...
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Within-host diversity of MRSA antimicrobial resistances.
Published: May, 2015

Abstract: OBJECTIVES: MRSA is a major antimicrobial resistance (AMR) pathogen. The reservoir of infecting isolates is colonization, which is the site of evolutionary selection. The aim was to identify if AMRs in colonizing MRSA populations diversified and p...
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The Basal Transcription Complex Component TAF3 Transduces Changes in Nuclear Phosphoinositides into Transcriptional Output.
Published: May, 2015

Abstract: Phosphoinositides (PI) are important signaling molecules in the nucleus that influence gene expression. However, if and how nuclear PI directly affects the transcriptional machinery is not known. We report that the lipid kinase PIP4K2B regulates n...
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Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC.
Published: May, 2015

Abstract: MYC is an oncoprotein transcription factor that is overexpressed in the majority of malignancies. The oncogenic potential of MYC stems from its ability to bind regulatory sequences in thousands of target genes, which depends on interaction of MYC ...
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Supp. informations: Interaction with WDR5 Promotes Target Gene Recognition and Tumorigenesis by MYC.
Published: May, 2015

Abstract: MYC is an oncoprotein transcription factor that is overexpressed in the majority of malignancies. The oncogenic potential of MYC stems from its ability to bind regulatory sequences in thousands of target genes, which depends on interaction of MYC ...
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A genomewide catalogue of single nucleotide polymorphisms in white-beaked and Atlantic white-sided dolphins
Published: May, 2015

Abstract: The field of population genetics is rapidly moving into population genomics as the quantity of data generated by high-throughput sequencing platforms increases. In this study, we used restriction-site-associated DNA sequencing (RADSeq) to recover ...
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Non-coding RNA Generated following Lariat Debranching Mediates Targeting of AID to DNA.
Published: May, 2015

Abstract: Transcription through immunoglobulin switch (S) regions is essential for class switch recombination (CSR), but no molecular function of the transcripts has been described. Likewise, recruitment of activation-induced cytidine deaminase (AID) to S r...
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Uvrag targeting by Mir125a and Mir351 modulates autophagy associated with Ewsr1 deficiency.
Published: May, 2015

Abstract: The EWSR1 (EWS RNA-binding protein 1/Ewing Sarcoma Break Point Region 1) gene encodes a RNA/DNA binding protein that is ubiquitously expressed and involved in various cellular processes. EWSR1 deficiency leads to impairment of development and acce...
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Evidence Supporting a Role for TopBP1 and Brd4 in the Initiation but Not Continuation of Human Papillomavirus 16 E1/E2-Mediated DNA Replication.
Published: May, 2015

Abstract: UNLABELLED: To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with hos...
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Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity.
Published: May, 2015

Abstract: Constitutively active MYC and reactivated telomerase often coexist in cancers. While reactivation of telomerase is thought to be essential for replicative immortality, MYC, in conjunction with cofactors, confers several growth advantages to cancer...
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Clinical application of whole-genome sequencing to inform treatment for multidrug-resistant tuberculosis cases.
Published: May, 2015

Abstract: The treatment of drug-resistant tuberculosis cases is challenging, as drug options are limited, and the existing diagnostics are inadequate. Whole-genome sequencing (WGS) has been used in a clinical setting to investigate six cases of suspected ex...
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Sensitive detection of chromatin-altering polymorphisms reveals autoimmune disease mechanisms.
Published: May, 2015

Abstract: Most disease associations detected by genome-wide association studies (GWAS) lie outside coding genes, but very few have been mapped to causal regulatory variants. Here, we present a method for detecting regulatory quantitative trait loci (QTLs) t...
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Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum.
Published: May, 2015

Abstract: To identify chromatin mechanisms of neuronal differentiation, we characterized chromatin accessibility and gene expression in cerebellar granule neurons (CGNs) of the developing mouse. We used DNase-seq to map accessibility of cis-regulatory eleme...
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A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature.
Published: May, 2015

Abstract: Alternative pre-mRNA splicing is a highly cell type-specific process essential to generating protein diversity. However, the mechanisms responsible for the establishment and maintenance of heritable cell-specific alternative-splicing programs are ...
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Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.
Published: May, 2015

Abstract: Technologies that enable targeted manipulation of epigenetic marks could be used to precisely control cell phenotype or interrogate the relationship between the epigenome and transcriptional control. Here we describe a programmable, CRISPR-Cas9-ba...
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C2H2 zinc finger proteins greatly expand the human regulatory lexicon.
Published: May, 2015

Abstract: Cys2-His2 zinc finger (C2H2-ZF) proteins represent the largest class of putative human transcription factors. However, for most C2H2-ZF proteins it is unknown whether they even bind DNA or, if they do, to which sequences. Here, by combining data f...
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Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral CD8+ T cell responses.
Published: May, 2015

Abstract: Successfully fighting infection requires a properly tuned immune system. Recent epidemiological studies link exposure to pollutants that bind the aryl hydrocarbon receptor (AHR) during development with poorer immune responses later in life. Yet, h...
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Global regulation of heterochromatin spreading by Leo1.
Published: May, 2015

Abstract: Heterochromatin plays important roles in eukaryotic genome regulation. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates robust mechanisms to contain heterochromatin within defined bounda...
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Development of microsatellite primers in the protected species Viola elatior (Violaceae) using next-generation sequencing.
Published: May, 2015

Abstract: PREMISE OF THE STUDY: Viola elatior (Violaceae) is a Eurasian perennial plant species in which French populations are threatened by anthropogenic pressures. Microsatellite primers were developed to investigate its genetic structure and diversity. ...
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The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding.
Published: April, 2015

Abstract: To effectively modulate the gene expression within an infected mammalian cell, the pathogen Mycobacterium tuberculosis would need to bring about epigenetic modifications at appropriate genomic loci. Working on this hypothesis, we show in this stud...
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Truncated HBx-dependent silencing of GAS2 promotes hepatocarcinogenesis through deregulation of cell cycle, senescence and p53-mediated apoptosis
Published: April, 2015

Abstract: Hepatocellular carcinoma (HCC) is a worldwide threat to public health, especially in China, where chronic hepatitis B virus (HBV) infection is found in 80-90% of all HCCs. The HBV-encoded X antigen (HBx) is a trans-regulatory protein involved in v...
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Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation.
Published: April, 2015

Abstract: Inflammation is a beneficial host response to infection but can contribute to inflammatory disease if unregulated. The Th17 lineage of T helper (Th) cells can cause severe human inflammatory diseases. These cells exhibit both instability (they can...
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Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling.
Published: April, 2015

Abstract: A bimodal switch model is widely used to describe transcriptional regulation by the thyroid hormone receptor (TR). In this model, the unliganded TR forms stable, chromatin-bound complexes with transcriptional co-repressors to repress transcription...
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Spt6 Is Essential for rRNA Synthesis by RNA Polymerase I
Published: April, 2015

Abstract: Spt6 has many roles in transcription initiation and elongation by RNA polymerase (Pol) II. These effects are mediated through interactions with histones, transcription factors, and the RNA polymerase. Two lines of evidence suggest that Spt6 also p...
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Suppression of Interferon β gene transcription by inhibitors of Bromodomain and Extra-Terminal (BET) family members.
Published: April, 2015

Abstract: Polo-Like Kinase (PLK) inhibitors, such as BI-2536, have been reported to suppress interferon β (IFNβ) gene transcription induced by ligands that activate TLR3 and TLR4. Here, we report that BI-2536 is likely to exert this effect by preventing the...
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RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements.
Published: April, 2015

Abstract: In mouse embryonic cells, ligand-activated retinoic acid receptors (RARs) play a key role in inhibiting pluripotency-maintaining genes and activating some major actors of cell differentiation. To investigate the mechanism underlying this dual regu...
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Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells.
Published: April, 2015

Abstract: Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections, and comprise nearly 8% of the human genome. The most recently acquired human ERV is HERVK(HML-2), which repeatedly infected the primate lineage both before and after the...
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Sequencing of allotetraploid cotton (Gossypium hirsutum L. acc. TM-1) provides a resource for fiber improvement.
Published: April, 2015

Abstract: Upland cotton is a model for polyploid crop domestication and transgenic improvement. Here we sequenced the allotetraploid Gossypium hirsutum L. acc. TM-1 genome by integrating whole-genome shotgun reads, bacterial artificial chromosome (BAC)-end ...
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The chromatin Remodeler CHD8 is required for activation of progesterone receptor-dependent enhancers.
Published: April, 2015

Abstract: While the importance of gene enhancers in transcriptional regulation is well established, the mechanisms and the protein factors that determine enhancers activity have only recently begun to be unravelled. Recent studies have shown that progestero...
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Genome-Wide Analysis of Phosphorylated PhoP Binding to Chromosomal DNA Reveals Several Novel Features of the PhoPR-Mediated Phosphate Limitation Response in Bacillus subtilis.
Published: April, 2015

Abstract: UNLABELLED: The PhoPR two-component signal transduction system controls one of three responses activated by Bacillus subtilis to adapt to phosphate-limiting conditions (PHO response). The response involves the production of enzymes and transporter...
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High-throughput and quantitative assessment of enhancer activity in mammals by CapStarr-seq.
Published: April, 2015

Abstract: Cell-type specific regulation of gene expression requires the activation of promoters by distal genomic elements defined as enhancers. The identification and the characterization of enhancers are challenging in mammals due to their genome complexi...
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Transcriptional co-repressor function of the hippo pathway transducers YAP and TAZ.
Published: April, 2015

Abstract: YAP (yes-associated protein) and TAZ are oncogenic transcriptional co-activators downstream of the Hippo tumor-suppressor pathway. However, whether YAP and/or TAZ (YAP/TAZ) engage in transcriptional co-repression remains relatively unexplored. Her...
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Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain.
Published: April, 2015

Abstract: Embryogenesis requires the precise activation and repression of many transcriptional regulators. The Polycomb group proteins and the associated H3K27me3 histone mark are essential to maintain the inactive state of many of these genes. Mammalian Ho...
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Divergent androgen regulation of unfolded protein response pathways drives prostate cancer
Published: April, 2015

Abstract: The unfolded protein response (UPR) is a homeostatic mechanism to maintain endoplasmic reticulum (ER) function. The UPR is activated by various physiological conditions as well as in disease states, such as cancer. As androgens regulate secretion ...
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Impact of oxidative stress defense on bacterial survival and morphological change in Campylobacter jejuni under aerobic conditions.
Published: April, 2015

Abstract: Campylobacter jejuni, a microaerophilic foodborne pathogen, inescapably faces high oxygen tension during its transmission to humans. Thus, the ability of C. jejuni to survive under oxygen-rich conditions may significantly impact C. jejuni viabilit...
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The Paf1 complex represses small-RNA-mediated epigenetic gene silencing.
Published: April, 2015

Abstract: RNA interference (RNAi) refers to the ability of exogenously introduced double-stranded RNA to silence expression of homologous sequences. Silencing is initiated when the enzyme Dicer processes the double-stranded RNA into small interfering RNAs (...
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Draft genome sequences of 26 porphyromonas strains isolated from the canine oral microbiome.
Published: April, 2015

Abstract: We present the draft genome sequences for 26 strains of Porphyromonas (P. canoris, P. gulae, P. cangingavalis, P. macacae, and 7 unidentified) and an unidentified member of the Porphyromonadaceae family. All of these strains were isolated from the...
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Characterization of the transcriptome of nascent hair cells and identification of direct targets of the Atoh1 transcription factor.
Published: April, 2015

Abstract: Hair cells are sensory receptors for the auditory and vestibular system in vertebrates. The transcription factor Atoh1 is both necessary and sufficient for the differentiation of hair cells, and is strongly upregulated during hair-cell regeneratio...
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Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate.
Published: April, 2015

Abstract: The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator of the canonical NF-κB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex fu...
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Zinc regulates a switch between primary and alternative S18 ribosomal proteins in Mycobacterium tuberculosis.
Published: April, 2015

Abstract: The Mycobacterium tuberculosis genome encodes five putative 'alternative' ribosomal proteins whose expression is repressed at high Zn(2+) concentration. Each alternative protein has a primary homologue that is predicted to bind Zn(2+) . We hypothe...
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Phylogenomic analysis shows that Bacillus amyloliquefaciens subsp plantarum is a later heterotypic synonym of Bacillus methylotrophicus.
Published: April, 2015

Abstract: The rhizosphere isolated bacteria belonging to the Bacillus amyloliquefaciens subsp. plantarum and Bacillus methylotrophicus clades are an important group of strains that are used as plant growth promoters and antagonists of plant pathogens. These...
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Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing.
Published: April, 2015

Abstract: Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response ne...
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A Role for the Serine/Arginine-Rich (SR) Protein B52/SRSF6 in Cell Growth and Myc Expression in Drosophila.
Published: April, 2015

Abstract: Serine-/arginine-rich (SR) proteins are RNA-binding proteins that are primarily involved in alternative splicing. Expression of some SR proteins is frequently upregulated in tumors, and previous reports have demonstrated that these proteins can di...
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Effect of poly(ADP-ribose)polymerase and DNA topoisomerase I inhibitors on the p53/p63-dependent survival of carcinoma cells.
Published: April, 2015

Abstract: Depending on their genetic background (p53(wt) versus p53(null)), carcinoma cells are more or less sensitive to drug-induced cell cycle arrest and/or apoptosis. Among the members of the p53 family, p63 is characterized by two N-terminal isoforms, ...
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Resolving phylogenetic relationships of the recently radiated carnivorous plant genus Sarracenia using target enrichment.
Published: April, 2015

Abstract: The North American carnivorous pitcher plant genus Sarracenia (Sarraceniaceae) is a relatively young clade (
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Targeting the MLL complex in castration-resistant prostate cancer.
Published: April, 2015

Abstract: Resistance to androgen deprivation therapies and increased androgen receptor (AR) activity are major drivers of castration-resistant prostate cancer (CRPC). Although prior work has focused on targeting AR directly, co-activators of AR signaling, w...
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Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.
Published: April, 2015

Abstract: Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergisti...
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STAT3 and HIF1alpha Signalling Drives Oncogenic Cellular Phenotypes in Malignant Peripheral Nerve Sheath Tumors (MPNSTs).
Published: April, 2015

Abstract: Therapeutic options are limited for Neurofibromatosis type 1 (NF1) associated malignant peripheral nerve sheath tumours(MPNSTs) and clinical trials using drug agents have so far been unsuccessful. This lack of clinical success is likely attributed...
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Lipid-induced epigenomic changes in human macrophages identify a coronary artery disease-associated variant that regulates PPAP2B Expression through Altered C/EBP-beta binding.
Published: April, 2015

Abstract: Genome-wide association studies (GWAS) have identified over 40 loci that affect risk of coronary artery disease (CAD) and the causal mechanisms at the majority of loci are unknown. Recent studies have suggested that many causal GWAS variants influ...
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5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer.
Published: April, 2015

Abstract: BACKGROUND: The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferati...
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The epigenetic regulator G9a mediates tolerance to RNA virus infection in Drosophila.
Published: April, 2015

Abstract: Little is known about the tolerance mechanisms that reduce the negative effects of microbial infection on host fitness. Here, we demonstrate that the histone H3 lysine 9 methyltransferase G9a regulates tolerance to virus infection by shaping the r...
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Oxyntomodulin regulates resetting of the liver circadian clock by food
Published: March, 2015

Abstract: Circadian clocks coordinate 24-hr rhythms of behavior and physiology. In mammals, a master clock residing in the suprachiasmatic nucleus (SCN) is reset by the light-dark cycle, while timed food intake is a potent synchronizer of peripheral clocks ...
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GAGA Factor Maintains Nucleosome-Free Regions and Has a Role in RNA Polymerase II Recruitment to Promoters
Published: March, 2015

Abstract: Previous studies have shown that GAGA Factor (GAF) is enriched on promoters with paused RNA Polymerase II (Pol II), but its genome-wide function and mechanism of action remain largely uncharacterized. We assayed the levels of transcriptionally-eng...
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CXCR4 expression on pathogenic T cells facilitates their bone marrow infiltration in a mouse model of aplastic anemia.
Published: March, 2015

Abstract: Aplastic anemia (AA) is a disease characterized by T-cell-mediated destruction of bone marrow (BM) hematopoietic stem and progenitor cells. Physiologically, T cells migrate to the BM in response to chemokines, such as SDF-1α, the ligand for CXCR4....
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Induction of hematopoietic and endothelial cell program orchestrated by ETS transcription factor ER71/ETV2
Published: March, 2015

Abstract: The ETS factor ETV2 (aka ER71) is essential for the generation of the blood and vascular system, as ETV2 deficiency leads to a complete block in blood and endothelial cell formation and embryonic lethality in the mouse. However, the ETV2-mediated ...
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SINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation.
Published: March, 2015

Abstract: Short interspersed nuclear elements (SINEs), such as Alu, spread by retrotransposition, which requires their transcripts to be copied into DNA and then inserted into new chromosomal sites. This can lead to genetic damage through insertional mutage...
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Mitogenomic phylogeny of the common long-tailed macaque (Macaca fascicularis fascicularis).
Published: March, 2015

Abstract: BACKGROUND: Long-tailed macaques (Macaca fascicularis) are an important model species in biomedical research and reliable knowledge about their evolutionary history is essential for biomedical inferences. Ten subspecies have been recognized, of wh...
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Polyploidy can drive rapid adaptation in yeast.
Published: March, 2015

Abstract: Polyploidy is observed across the tree of life, yet its influence on evolution remains incompletely understood. Polyploidy, usually whole-genome duplication, is proposed to alter the rate of evolutionary adaptation. This could occur through comple...
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Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion.
Published: March, 2015

Abstract: Risk factors indicate the importance of oxidative stress during ovarian carcinogenesis. To tolerate oxidative stress, cells activate the transcription factor Nrf2 (Nfe2l2), the master regulator of antioxidant and cytoprotective genes. Indeed, for ...
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Evolution of the bamboos (Bambusoideae; Poaceae): a full plastome phylogenomic analysis.
Published: March, 2015

Abstract: BACKGROUND: Bambusoideae (Poaceae) comprise three distinct and well-supported lineages: tropical woody bamboos (Bambuseae), temperate woody bamboos (Arundinarieae) and herbaceous bamboos (Olyreae). Phylogenetic studies using chloroplast markers ha...
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Breeding scheme and maternal small RNAs affect the efficiency of transgenerational inheritance of a paramutation in mice.
Published: March, 2015

Abstract: Paramutations result from interactions between two alleles at a single locus, whereby one induces a heritable change in the other. Although common in plants, paramutations are rarely studied in animals. Here, we report a new paramutation mouse mod...
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Epigenetic modulation with HDAC inhibitor CG200745 induces anti-proliferation in non-small cell lung cancer cells.
Published: March, 2015

Abstract: Histone modification plays a pivotal role on gene regulation, as regarded as global epigenetic markers, especially in tumor related genes. Hence, chemical approaches targeting histone-modifying enzymes have emerged onto the main stage of anticance...
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Impact of Thyroid Hormones on Estrogen Receptor α-Dependent Transcriptional Mechanisms in Ventromedial Hypothalamus and Preoptic Area.
Published: March, 2015

Abstract: Elevated levels of thyroid hormones (TH) reduce estradiol (E2)-dependent female sexual behavior. E2 stimulates progesterone receptor (Pgr) and oxytocin receptor (Oxtr) within the ventromedial hypothalamus and preoptic area, critical hypothalamic n...
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Adipose tissue-derived stem cells from obese subjects contribute to inflammation and reduced insulin response in adipocytes through differential regulation of the Th1/Th17 balance and monocyte activation.
Published: March, 2015

Abstract: Obesity, through low-grade inflammation, can drive insulin-resistance and type 2 diabetes. While infiltration of adipose tissue (AT) with mononuclear cells (MNC) is well established in obesity, the functional consequences of these interactions are...
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The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3.
Published: March, 2015

Abstract: The NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes undergoing selection, and has been shown to control the development of Treg cells; however the role of Nr4a1 in CD8(+) T cells remains undefined. Here we report a nove...
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Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma.
Published: March, 2015

Abstract: Restoration of the antitumor activity of p53 could offer a promising approach for the treatment of neuroblastoma. MicroRNAs (miRNAs) are important mediators of p53 activity, but their role in the p53 response has not yet been comprehensively addre...
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Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency.
Published: March, 2015

Abstract: The mechanisms by which transcription factor haploinsufficiency alters the epigenetic and transcriptional landscape in human cells to cause disease are unknown. Here, we utilized human induced pluripotent stem cell (iPSC)-derived endothelial cells...
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H3K4me3 demethylation by the histone demethylase KDM5C/JARID1C promotes DNA replication origin firing.
Published: March, 2015

Abstract: DNA replication is a tightly regulated process that initiates from multiple replication origins and leads to the faithful transmission of the genetic material. For proper DNA replication, the chromatin surrounding origins needs to be remodeled. Ho...
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Identification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia.
Published: March, 2015

Abstract: Despite recent advances in the cure rate of acute lymphoblastic leukaemia (ALL), the prognosis for patients with relapsed ALL remains poor. Here we identify FOXM1 as a candidate responsible for an aggressive clinical course. We show that FOXM1 lev...
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PW1/Peg3 expression regulates key properties that determine mesoangioblast stem cell competence.
Published: March, 2015

Abstract: Mesoangioblasts are vessel-associated progenitor cells that show therapeutic promise for the treatment of muscular dystrophy. Mesoangioblasts have the ability to undergo skeletal muscle differentiation and cross the blood vessel wall regardless of...
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AtEAF1 is a potential platform protein for Arabidopsis NuA4 acetyltransferase complex.
Published: March, 2015

Abstract: BACKGROUND: Histone acetyltransferase complex NuA4 and histone variant exchanging complex SWR1 are two chromatin modifying complexes which act cooperatively in yeast and share some intriguing structural similarities. Protein subunits of NuA4 and S...
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Nuclear matrix binding protein SMAR1 regulates T-cell differentiation and allergic airway disease.
Published: March, 2015

Abstract: Asthma is a complex airway allergic disease involving the interplay of various cell types, cytokines, and transcriptional factors. Though many factors contribute to disease etiology, the molecular control of disease phenotype and responsiveness is...
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Genome-wide mapping reveals conservation of promoter DNA methylation following chicken domestication.
Published: March, 2015

Abstract: It is well-known that environment influences DNA methylation, however, the extent of heritable DNA methylation variation following animal domestication remains largely unknown. Using meDIP-chip we mapped the promoter methylomes for 23,316 genes in...
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Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells
Published: March, 2015

Abstract: DNA methylation is thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells (DCs) with a pathogenic bacteria is associated with rapid chang...
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Population differentiation determined from putative neutral and divergent adaptive genetic markers in Eulachon (Thaleichthys pacificus, Osmeridae), an anadromous Pacific smelt.
Published: March, 2015

Abstract: Twelve eulachon (Thaleichthys pacificus, Osmeridae) populations ranging from Cook Inlet, Alaska and along the west coast of North America to the Columbia River were examined by restriction-site-associated DNA (RAD) sequencing to elucidate patterns...
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Taspase1-dependent TFIIA cleavage coordinates head morphogenesis by limiting Cdkn2a locus transcription.
Published: March, 2015

Abstract: Head morphogenesis requires complex signal relays to enable precisely coordinated proliferation, migration, and patterning. Here, we demonstrate that, during mouse head formation, taspase1-mediated (TASP1-mediated) cleavage of the general transcri...
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Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells.
Published: March, 2015

Abstract: Replication fork reversal protects forks from breakage after poisoning of Topoisomerase 1. We here investigated fork progression and chromosomal breakage in human cells in response to a panel of sublethal genotoxic treatments, using other topoisom...
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Exon-intron circular RNAs regulate transcription in the nucleus.
Published: March, 2015

Abstract: Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression. A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA...
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Essential role of the iron-sulfur cluster binding domain of the primase regulatory subunit Pri2 in DNA replication initiation.
Published: March, 2015

Abstract: DNA primase catalyzes de novo synthesis of a short RNA primer that is further extended by replicative DNA polymerases during initiation of DNA replication. The eukaryotic primase is a heterodimeric enzyme comprising a catalytic subunit Pri1 and a ...
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The Integrator complex controls the termination of transcription at diverse classes of gene targets.
Published: March, 2015

Abstract: Complexes containing INTS3 and either NABP1 or NABP2 were initially characterized in DNA damage responses, but their biochemical function remained unknown. Using affinity purifications and HIV Integration targeting-sequencing (HIT-Seq), we find th...
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The DREAM complex promotes gene body H2A.Z for target repression.
Published: March, 2015

Abstract: The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell cycle genes, but its mechanism of action is poorly understood. Here we show that Caenorhabditis elegans DREAM targets have an unusual p...
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Genome-wide redistribution of BRD4 binding sites in transformation resistant cells.
Published: March, 2015

Abstract: Hutchinson-Gilford progeria syndrome (HGPS) patients do not develop cancer despite a significant accumulation of DNA damage in their cells. We have recently reported that HGPS cells are refractory to experimental oncogenic transformation and we id...
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The histone chaperone complex HIR *maintains *nucleosome occupancy and counterbalances impaired histone deposition in CAF-1 mutants.
Published: March, 2015

Abstract: Chromatin organization is essential for coordinated gene expression, genome stability, and inheritance of epigenetic information. Main components of chromatin assembly are specific complexes such as CHROMATIN ASSEMBLY FACTOR 1 (CAF-1) and HISTONE ...
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FUBP1: a new protagonist in splicing regulation of the DMD gene.
Published: February, 2015

Abstract: We investigated the molecular mechanisms for in-frame skipping of DMD exon 39 caused by the nonsense c.5480T>A mutation in a patient with Becker muscular dystrophy. RNase-assisted pull down assay coupled with mass spectrometry revealed that the mu...
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Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy
Published: February, 2015

Abstract: To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mu- cosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts o...
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Genome-wide profiling of DNA methylation provides insights into epigenetic regulation of fungal development in a plant pathogenic fungus, Magnaporthe oryzae.
Published: February, 2015

Abstract: DNA methylation is an important epigenetic modification that regulates development of plants and mammals. To investigate the roles of DNA methylation in fungal development, we profiled genome-wide methylation patterns at single-nucleotide resoluti...
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A Meier-Gorlin Syndrome Mutation Impairs the ORC1-Nucleosome Association.
Published: February, 2015

Abstract: Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the...
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MCPH1 maintains long-term epigenetic silencing of ANGPT2 in chronic lymphocytic leukemia.
Published: February, 2015

Abstract: The microcephalin gene (MCPH1) [also known as inhibitor of human telomerase reverse transcriptase (hTERT) expression] is a tumor suppressor gene that is functionally involved in the DNA damage response. Angiopoietin 2 (ANGPT2) is a crucial factor ...
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Silica nanoparticles induce oxidative stress, inflammation, and endothelial dysfunction in vitro via activation of the MAPK/Nrf2 pathway and nuclear factor-κB signaling.
Published: February, 2015

Abstract: Abstract: Despite the widespread application of silica nanoparticles (SiNPs) in industrial, commercial, and biomedical fields, their response to human cells has not been fully elucidated. Overall, little is known about the toxicological effec...
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Intermediate DNA methylation is a conserved signature of genome regulation.
Published: February, 2015

Abstract: The role of intermediate methylation states in DNA is unclear. Here, to comprehensively identify regions of intermediate methylation and their quantitative relationship with gene activity, we apply integrative and comparative epigenomics to 25 hum...
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Epigenetic and transcriptional determinants of the human breast.
Published: February, 2015

Abstract: While significant effort has been dedicated to the characterization of epigenetic changes associated with prenatal differentiation, relatively little is known about the epigenetic changes that accompany post-natal differentiation where fully funct...
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MEK guards proteome stability and inhibits tumor-suppressive amyloidogenesis via HSF1.
Published: February, 2015

Abstract: Signaling through RAS/MAP kinase pathway is central to biology. ERK has long been perceived as the only substrate for MEK. Here, we report that HSF1, the master regulator of the proteotoxic stress response, is a new MEK substrate. Beyond mediating...
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p73 engages A2B receptor signalling to prime cancer cells to chemotherapy-induced death.
Published: February, 2015

Abstract: Tumour cells often acquire the ability to escape cell death, a key event leading to the development of cancer. In almost half of all human cancers, the capability to induce cell death is reduced by the mutation and inactivation of p53, a tumour su...
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Phylogenomics of Phrynosomatid Lizards: Conflicting Signals from Sequence Capture versus Restriction Site Associated DNA Sequencing
Published: February, 2015

Abstract: Sequence capture and restriction site associated DNA sequencing (RADseq) are popular methods for obtaining large numbers of loci for phylogenetic analysis. These methods are typically used to collect data at different evolutionary timescales; sequ...
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The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65.
Published: February, 2015

Abstract: The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-...
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Circulating nucleic acids damage DNA of healthy cells by integrating into their genomes
Published: February, 2015

Abstract: Whether nucleic acids that circulate in blood have any patho-physiological functions in the host have not been explored.We report here that far from being inert molecules, circulating nucleic acids have significant biological activities of their o...
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Single-Base Resolution Analysis of 5-Formyl and 5-Carboxyl Cytosine Reveals Promoter DNA Methylation Dynamics.
Published: February, 2015

Abstract: Ten eleven translocation (Tet) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC can be further excised by thymine-DNA glycosylase (Tdg). Here, we present...
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Genipin as a novel chemical activator of EBV lytic cycle.
Published: February, 2015

Abstract: Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be ...
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Discovery of transcription factors and regulatory regions driving in vivo tumor development by ATAC-seq and FAIRE-seq open chromatin profiling.
Published: February, 2015

Abstract: Genomic enhancers regulate spatio-temporal gene expression by recruiting specific combinations of transcription factors (TFs). When TFs are bound to active regulatory regions, they displace canonical nucleosomes, making these regions biochemically...
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Increased HDAC3 and decreased miRNA-130a expression in PBMCs through recruitment HDAC3 in patients with spinal cord injuries
Published: February, 2015

Abstract: The study was performed to investigate the molecular mechanism for SCI patients. The interaction between miRNA-130a and HDAC was demonstrated in PBMCs from SCI patients. Increased HDAC3 and decreased miRNA-130a were observed in PBMCs from AS patie...
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Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli.
Published: February, 2015

Abstract: Escherichia coli endoribonuclease E has a major influence on gene expression. It is essential for the maturation of ribosomal and transfer RNA as well as the rapid degradation of messenger RNA. The latter ensures that translation closely follows p...
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Tat predominantly associates with host promoter elements in HIV-1-infected T-cells - regulatory basis of transcriptional repression of c-Rel.
Published: February, 2015

Abstract: UNLABELLED: HIV-1 Tat is a multifunctional regulatory protein that, in addition to its primary function of transactivating viral transcription, also tends to modulate cellular gene expression, for which the molecular mechanism remains to be clarif...
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Polycomb YY1 is a critical interface between epigenetic code and miRNA machinery after exposure to hypoxia in malignancy.
Published: January, 2015

Abstract: Yin Yang 1 (YY1) is a member of polycomb protein family involved in epigenetic modifications and transcriptional controls. We have shown that YY1 acts as positive regulator of tumor growth and angiogenesis by interfering with the VEGFA network. Ye...
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Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan.
Published: January, 2015

Abstract: Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is unclear. Here, we show that reduced levels of th...
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Curcumin inhibits anchorage-independent growth of HT29 human colon cancer cells by targeting epigenetic restoration of the tumor suppressor gene DLEC1.
Published: January, 2015

Abstract: Colorectal cancer remains the most prevalent malignancy in humans. The impact of epigenetic alterations on the development of this complex disease is now being recognized. The dynamic and reversible nature of epigenetic modifications makes them a ...
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Reduced Expression of MYC Increases Longevity and Enhances Healthspan.
Published: January, 2015

Abstract: MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including ...
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Ligand-dependent enhancer activation regulated by topoisomerase-I activity.
Published: January, 2015

Abstract: The discovery that enhancers are regulated transcription units, encoding eRNAs, has raised new questions about the mechanisms of their activation. Here, we report an unexpected molecular mechanism that underlies ligand-dependent enhancer activatio...
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A small peptide derived from p53 linker region can resume the apoptotic activity of p53 by sequestering iASPP with p53.
Published: January, 2015

Abstract: One of the most important tumor suppression functions of p53 is its ability to induce apoptosis. iASPP is an inhibitory member of the ASPP protein family. It can specifically inhibit the normal function of p53 as a suppressor. The mechanism of iAS...
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Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling.
Published: January, 2015

Abstract: Ovarian clear-cell carcinoma (OCCC) is an aggressive form of ovarian cancer with high ARID1A mutation rates. Here we present a mutant mouse model of OCCC. We find that ARID1A inactivation is not sufficient for tumour formation, but requires concur...
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Age dependent changes in the LPS induced transcriptome of bovine dermal fibroblasts occurs without major changes in the methylome.
Published: January, 2015

Abstract: BackgroundBy comparing fibroblasts collected from animals at 5-months or 16-months of age we have previously found that the cultures from older animals produce much more IL-8 in response to lipopolysaccharide (LPS) stimulation. We now expand this ...
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Pharmacologically relevant doses of valproate upregulate CD20 expression in three diffuse large B-cell lymphoma patients in vivo
Published: January, 2015

Abstract: Background Epigenetic code modifications by histone deacetylase inhibitors (HDACi) have been proposed as potential new therapies for lymphoid malignancies. Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma for ...
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Dppa3 expression is critical for generation of fully reprogrammed iPS cells and maintenance of Dlk1-Dio3 imprinting.
Published: January, 2015

Abstract: Reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs) often generates partially reprogrammed iPSCs (pre-iPSCs), low-grade chimera forming iPSCs (lg-iPSCs) and fully reprogrammed, high-grade chimera production competent i...
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Genome-wide DNA methylation analysis in Graves' disease.
Published: January, 2015

Abstract: As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathoge...
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Dynamic Regulation of Schwann Cell Enhancers after Peripheral Nerve Injury.
Published: January, 2015

Abstract: Myelination of the peripheral nervous system is required for axonal function and long term stability. After peripheral nerve injury, Schwann cells transition from axon myelination to a demyelinated state that supports neuronal survival and ultimat...
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An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations.
Published: January, 2015

Abstract: Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required t...
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USP7 COOPERATES WITH SCML2 TO REGULATE THE ACTIVITY OF PRC1.
Published: January, 2015

Abstract: USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of the Polycomb Repressive Complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by th...
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Alternative splicing regulates the expression of G9A and SUV39H2 methyltransferases, and dramatically changes SUV39H2 functions.
Published: January, 2015

Abstract: Alternative splicing is the main source of proteome diversity. Here, we have investigated how alternative splicing affects the function of two human histone methyltransferases (HMTase): G9A and SUV39H2. We show that exon 10 in G9A and exon 3 in SU...
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Linked circadian outputs control elongation growth and flowering in response to photoperiod and temperature
Published: January, 2015

Abstract: Clock-regulated pathways coordinate the response of many developmental processes to changes in photoperiod and temperature. We model two of the best-understood clock output pathways in Arabidopsis, which control key regulators of flowering and elo...
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PU.1 Opposes IL-7-Dependent Proliferation of Developing B Cells with Involvement of the Direct Target Gene Bruton Tyrosine Kinase.
Published: January, 2015

Abstract: Deletion of genes encoding the E26 transformation-specific transcription factors PU.1 and Spi-B in B cells (CD19-CreΔPB mice) leads to impaired B cell development, followed by B cell acute lymphoblastic leukemia at 100% incidence and with a median...
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Transcription-coupled recruitment of human CHD1 and CHD2 influences chromatin accessibility and histone H3 and H3.3 occupancy at active chromatin regions
Published: January, 2015

Abstract: Background CHD1 and CHD2 chromatin remodeling enzymes play important roles in development, cancer and differentiation. At a molecular level, the mechanisms are not fully understood but include transcriptional regulation, nucleosome organization a...
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Recurrent ETNK1 mutations in atypical chronic myeloid leukemia.
Published: January, 2015

Abstract: Despite the recent identification of recurrent SETBP1 mutations in atypical chronic myeloid leukemia (aCML), a complete description of the somatic lesions responsible for the onset of this disorder is still lacking. To find additional somatic abno...
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The Integrase Cofactor LEDGF/p75 Associates with Iws1 and Spt6 for Postintegration Silencing of HIV-1 Gene Expression in Latently Infected Cells.
Published: January, 2015

Abstract: The persistence of a latent reservoir containing transcriptionally silent, but replication-competent, integrated provirus is a serious challenge to HIV eradication. HIV integration is under the control of LEDGF/p75, the cellular cofactor of viral ...
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Htt CAG repeat expansion confers pleiotropic gains of mutant huntingtin function in chromatin regulation
Published: January, 2015

Abstract: The CAG repeat expansion in the Huntington's disease gene HTT extends a polyglutamine tract in mutant huntingtin that enhances its ability to facilitate polycomb repressive complex 2 (PRC2). To gain insight into this dominant gain of function, we ...
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Genetic evidence for ecological divergence in kokanee salmon.
Published: January, 2015

Abstract: The evolution of locally adapted phenotypes among populations that experience divergent selective pressures is a central mechanism for generating and maintaining biodiversity. Recently, the advent of high-throughput DNA sequencing technology has p...
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Thyroid hormone receptor sumoylation is required for preadipocyte differentiation and proliferation.
Published: January, 2015

Abstract: Thyroid hormone and thyroid hormone receptor (TR) play an essential role in metabolic regulation. However, the role of TR in adipogenesis is not established. We previously reported that TR sumoylation is essential for TR-mediated gene regulation a...
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Phosphorylation of TET proteins is regulated via O-GlcNAcylation by the glycosyltransferase OGT.
Published: January, 2015

Abstract: TET proteins oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC) and 5-carboxylcytosine (caC) and thus provide a possible means for active DNA demethylation in mammals. Although their catalytic mechanism is well c...
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STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral activity in the absence of STAT1.
Published: January, 2015

Abstract: Evidence is accumulating for the existence of a STAT2/IRF9-dependent, STAT1-independent IFNα signaling pathway. However, no detailed insight exists in the genome-wide transcriptional regulation and the biological implications of STAT2/IRF9 depende...
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NTR1 is required for transcription elongation checkpoints at alternative exons in Arabidopsis
Published: January, 2015

Abstract: The interconnection between transcription and splicing is a subject of intense study. We report that Arabidopsis homologue of spliceosome disassembly factor NTR1 is required for correct expression and splicing of DOG1, a regulator of seed dormancy...
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Locus-Specific Targeting to the X Chromosome Revealed by the RNA Interactome of CTCF.
Published: January, 2015

Abstract: CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X chromosome inactivation (XCI)...
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Genome-wide methylation analysis in Silver-Russell syndrome patients.
Published: January, 2015

Abstract: Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised by severe in utero growth restriction and poor postnatal growth, body asymmetry, irregular craniofacial features and several additional minor malformations. The aet...
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The human urine virome in association with urinary tract infections
Published: January, 2015

Abstract: While once believed to represent a sterile environment, the human urinary tract harbors a unique cellular microbiota. We sought to determine whether the human urinary tract also is home to viral communities whose membership might reflect urinary t...
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STAT3 acts through pre-existing nucleosome-depleted regions bound by FOS during an epigenetic switch linking inflammation to cancer.
Published: January, 2015

Abstract: BACKGROUND: Transient induction of the Src oncoprotein in a non-transformed breast cell line can initiate an epigenetic switch to a cancer cell via a positive feedback loop that involves activation of the signal transducer and activator of transcr...
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Amplification of pico-scale DNA mediated by bacterial carrier DNA for small-cell-number transcription factor ChIP-seq.
Published: January, 2015

Abstract: BACKGROUND: Chromatin-Immunoprecipitation coupled with deep sequencing (ChIP-seq) is used to map transcription factor occupancy and generate epigenetic profiles genome-wide. The requirement of nano-scale ChIP DNA for generation of sequencing libra...
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Histone H3 Phosphorylation in GBM: a New Rational to Guide the Use of Kinase Inhibitors in anti-GBM Therapy
Published: January, 2015

Abstract: Histones post-translational modifications (PTMs) are crucial components of diverse processes that modulate chromatin. Among the histones PTMs, the histones phosphorylation appears such crucial since it plays a significant role into DNA repair stru...
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Prolonged TNFα primes fibroblast-like synoviocytes in a gene-specific manner by altering chromatin.
Published: January, 2015

Abstract: Objective: During the course of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) are chronically exposed to an inflammatory milieu. In the current study we test the hypothesis that chronic exposure of FLS to TNFα augments inflammatory ...
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Trichoderma reesei meiosis generates segmentally aneuploid progeny with higher xylanase-producing capability.
Published: January, 2015

Abstract: BACKGROUND: Hypocrea jecorina is the sexual form of the industrial workhorse fungus Trichoderma reesei that secretes cellulases and hemicellulases to degrade lignocellulosic biomass into simple sugars, such as glucose and xylose. H. jecorina CBS99...
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CpG signalling, H2A.Z/H3 acetylation and microRNA-mediated deferred self-attenuation orchestrate foetal NOS3 expression.
Published: January, 2015

Abstract: BACKGROUND: An adverse intrauterine environment leads to permanent physiological changes including vascular tone regulation, potentially influencing the risk for adult vascular diseases. We therefore aimed to monitor responsive NOS3 expression in ...
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Genome-wide comparison of PU.1 and Spi-B binding sites in a mouse B lymphoma cell line.
Published: January, 2015

Abstract: BACKGROUND: Spi-B and PU.1 are highly related members of the E26-transformation-specific (ETS) family of transcription factors that have similar, but not identical, roles in B cell development. PU.1 and Spi-B are both expressed in B cells, and hav...
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ERK signaling regulates opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.
Published: January, 2015

Abstract: JUN transcription factors bind DNA as part of the AP-1 complex, regulate many cellular processes, and play a key role in oncogenesis. The three JUN proteins (c-JUN, JUNB, and JUND) can have both redundant and unique functions depending on the biol...
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Initiation and maintenance of pluripotency gene expression in the absence of cohesin.
Published: January, 2015

Abstract: Cohesin is implicated in establishing and maintaining pluripotency. Whether this is because of essential cohesin functions in the cell cycle or in gene regulation is unknown. Here we tested cohesin's contribution to reprogramming in systems that r...
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Locus-specific DNA methylation analysis of retrotransposons in ES, somatic and cancer cells using High-Throughput Targeted Repeat Element Bisulfite Sequencing
Published: January, 2015

Abstract: DNA methylation is a major epigenetic mark associated with multiple aspects of retrotransposons within the mammalian genome. In order to study DNA methylation of a large number of retrotransposons on an individual-locus basis, we have developed a ...
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Extracellular signal-related kinase 2/specificity protein 1/specificity protein 3/repressor element-1 silencing transcription factor pathway is involved in Aroclor 1254-induced toxicity in SH-SY5Y neuronal cells.
Published: January, 2015

Abstract: Polychlorinated biphenyls (PCBs) cause a wide spectrum of toxic effects in the brain through undefined mechanisms. Exposure to the PCB mixture Aroclor-1254 (A1254) increases the repressor element-1 silencing transcription factor (REST) expression,...
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Sequencing, identification and mapping of primed L1 elements (SIMPLE) reveals significant variation in full length L1 elements between individuals.
Published: January, 2015

Abstract: BACKGROUND: There are over a half a million copies of L1 retroelements in the human genome which are responsible for as much as 0.5% of new human genetic diseases. Most new L1 inserts arise from young source elements that are polymorphic in the hu...
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BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence.
Published: January, 2015

Abstract: Prostate cancer is driven by a combination of genetic and/or epigenetic alterations. Epigenetic alterations are frequently observed in all human cancers, yet how aberrant epigenetic signatures are established is poorly understood. Here we show tha...
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An integrated functional genomic analysis identifies the antitumorigenic mechanism of action for PPARγ in lung cancer cells
Published: January, 2015

Abstract: Integrating the analysis of the cistrome of a transcription factor by ChIP-Seq with the study of its transcriptional output by microarray or RNA-Seq analysis is a powerful approach to elucidate the genomic functions of a tran- scriptionfactor. Rec...
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Ezh2 represses the basal cell lineage during lung endoderm development.
Published: January, 2015

Abstract: The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion rem...
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Transcriptomic profiles of aging in purified human immune cells.
Published: January, 2015

Abstract: BACKGROUND: Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell ty...
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Transcriptional complexity and roles of Fra-1/AP-1 at the uPA/Plau locus in aggressive breast cancer.
Published: January, 2015

Abstract: Plau codes for the urokinase-type plasminogen activator (uPA), critical in cancer metastasis. While the mechanisms driving its overexpression in tumorigenic processes are unknown, it is regulated by the AP-1 transcriptional complex in diverse situ...
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Molecular and Biochemical Characterization of a Novel Multidomain Xylanase from Arthrobacter sp. GN16 Isolated from the Feces of Grus nigricollis.
Published: January, 2015

Abstract: A novel glycosyl hydrolase family 10 (GH 10) xylanase (XynAGN16), consisting of five domains, was revealed from the genome sequence of Arthrobacter sp. GN16 isolated from the feces of Grus nigricollis. XynAGN16 and its truncated derivatives XynAGN...
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DNA Methylation Analysis of the Macrosatellite Repeat Associated with FSHD Muscular Dystrophy at Single Nucleotide Level.
Published: December, 2014

Abstract: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited diseases of the skeletal muscle. It is characterized by asymmetric muscle weakness and variable penetrance. FSHD is linked to a reduction in copy number of the D4Z4 ...
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Paclitaxel resistance increases oncolytic adenovirus efficacy via upregulated CAR expression and dysfunctional cell cycle control.
Published: December, 2014

Abstract: Resistance to paclitaxel chemotherapy frequently develops in ovarian cancer. Oncolytic adenoviruses are a novel therapy for human malignancies that are being evaluated in early phase trials. However, there are no reliable predictive biomarkers for...
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A novel Cd8-cis-regulatory element preferentially directs expression in CD44hiCD62L+ CD8+ T cells and in CD8αα+ dendritic cells.
Published: December, 2014

Abstract: CD8 coreceptor expression is dynamically regulated during thymocyte development and is tightly controlled by the activity of at least 5 different cis-regulatory elements. Despite the detailed characterization of the Cd8 loci, the regulation of the...
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Epigenetic modification of the PD-1 (Pdcd1) promoter in effector CD4(+) T cells tolerized by peptide immunotherapy.
Published: December, 2014

Abstract: Clinically effective antigen-based immunotherapy must silence antigen-experienced effector T cells (Teff) driving ongoing immune pathology. Using CD4(+) autoimmune Teff cells, we demonstrate that peptide immunotherapy (PIT) is strictly dependent u...
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Cryosectioning the intestinal crypt-villus axis: an ex vivo method to study the dynamics of epigenetic modifications from stem cells to differentiated cells
Published: December, 2014

Abstract: The intestinal epithelium is a particularly attractive biological adult model to study epigenetic mechanisms driving adult stem cell renewal and cell differentiation. Since epigenetic modifications are dynamic, we have developed an original ex viv...
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Whole-exome sequencing identify a new mutation of MYH7 in a Chinese family with left ventricular noncompaction.
Published: December, 2014

Abstract: BACKGROUND: Left ventricular noncompaction (LVNC) is a genetic cardiomyopathy results from the failure of myocardial development during embryogenesis. Previous reports show that defects in TAZ, SCN5A, TPM1, YWHAE, MYH7, ACTC1 and TNNT2 are associa...
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ChIPping Away at the Drosophila Clock
Published: December, 2014

Abstract: In eukaryotes, the circadian clock controls 24 h rhythms in physiology, metabolism, and behavior via cell autonomous transcriptional feedback loops. These feedback loops keep circadian time and control rhythmic outputs by driving rhythms in transc...
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Methods to Study Molecular Mechanisms of the Neurospora Circadian Clock
Published: December, 2014

Abstract: Eukaryotic circadian clocks are comprised of interlocked autoregulatory feedback loops that control gene expression at the levels of transcription and translation. The filamentous fungus Neurospora crassa is an excellent model for the complex mole...
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Purification and Analysis of PERIOD Protein Complexes of the Mammalian Circadian Clock
Published: December, 2014

Abstract: In mammals, circadian rhythms are generated at least in part by a cell-autonomous transcriptional feedback loop in which the three PERIOD (PER) and two CRYPTOCHROME (CRY) proteins inhibit the activity of the dimeric transcription factor CLOCK-BMAL...
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Next-generation sequencing workflow for assembly of non-model mitogenomes exemplified with North Pacific Albatrosses (Phoebastria spp.).
Published: December, 2014

Abstract: Use of complete mitochondrial genomes (mitogenomes) can greatly increase the resolution achievable in phylogeographic and historical demographic studies. Using next generation sequencing methods, it is now feasible to efficiently sequence mitogeno...
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Cold acclimation induces distinctive changes in the chromatin state and transcript levels of COR genes in Cannabis sativa varieties with contrasting cold acclimation capacities.
Published: December, 2014

Abstract: Little is known about the capacity of Cannabis sativa to cold acclimate and develop freezing tolerance. This study investigates the cold acclimation capacity of nine C. sativa varieties and the underlying genetic and epigenetic responses. The vari...
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NCOA3-mediated upregulation of mucin expression via transcriptional and post-translational changes during the development of pancreatic cancer.
Published: December, 2014

Abstract: Pancreatic cancer (PC) is characterized by aberrant overexpression of mucins that contribute to its pathogenesis. Although the inflammatory cytokines contribute to mucin overexpression, the mucin profile of PC is markedly distinct from that of nor...
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Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas.
Published: December, 2014

Abstract: In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome / HNPCC, no germline alteration in the APC, MUTYH, or mismatch repair (MMR) genes are found. Missense mutations in the polymerase genes POLE and POLD1 have r...
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RNA Chromatin Immunoprecipitation (RNA-ChIP) in Caenorhabditis elegans
Published: December, 2014

Abstract: The RNA chromatin immunoprecipitation assay (RNA-ChIP) allows detection and quantification of RNA–protein interactions using in vivo cross-linking with formaldehyde followed by immunoprecipitation of the RNA–protein complexes. Here we describe th...
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Activation of aryl hydrocarbon receptor promotes invasion of clear cell renal cell carcinoma and is associated with poor prognosis and cigarette smoke.
Published: December, 2014

Abstract: Although exposure to environmental pollutants is one of the risk factors for renal cell carcinoma (RCC), its relationship with carcinogenesis and the progression of RCC remains unknown. The present study was designed to elucidate the role of the a...
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Modulation of p53 and met expression by Krüppel-like factor 8 regulates zebrafish cerebellar development.
Published: December, 2014

Abstract: Krüppel-like factor 8 (Klf8) is a zinc-finger transcription factor implicated in cell proliferation, and cancer cell survival and invasion; however, little is known about its role in normal embryonic development. Here, we show that Klf8 is re...
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Product Binding Enforces the Genomic Specificity of a Yeast Polycomb Repressive Complex.
Published: December, 2014

Abstract: We characterize the Polycomb system that assembles repressive subtelomeric domains of H3K27 methylation (H3K27me) in the yeast Cryptococcus neoformans. Purification of this PRC2-like protein complex reveals orthologs of animal PRC2 components as w...
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An AUTS2-Polycomb complex activates gene expression in the CNS.
Published: December, 2014

Abstract: Naturally occurring variations of Polycomb repressive complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, autism susceptibility candidate 2 (AUTS2). Although AUTS2 is often disrup...
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Plasmid Flux in Escherichia coli ST131 Sublineages, Analyzed by Plasmid Constellation Network (PLACNET), a New Method for Plasmid Reconstruction from Whole Genome Sequences.
Published: December, 2014

Abstract: Bacterial whole genome sequence (WGS) methods are rapidly overtaking classical sequence analysis. Many bacterial sequencing projects focus on mobilome changes, since macroevolutionary events, such as the acquisition or loss of mobile genetic eleme...
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A novel analytical brain block tool to enable functional annotation of discriminatory transcript biomarkers among discrete regions of the fronto-limbic circuit in primate brain.
Published: December, 2014

Abstract: Fronto-limbic circuits in the primate brain are responsible for executive function, learning and memory, and emotions, including fear. Consequently, changes in gene expression in cortical and subcortical brain regions housing these circuits are as...
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MiR-127 Modulates Macrophage Polarization and Promotes Lung Inflammation and Injury by Activating the JNK Pathway.
Published: December, 2014

Abstract: A polarized macrophage response is presumed to have a pivotal role in a variety of immunological pathophysiology. However, the molecular mechanism underlying macrophage functional shaping remains largely unknown. In this study, we reveal a pivotal...
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Histone Deacetylase 6 is a FoxO transcription factor-dependent effector in skeletal muscle atrophy.
Published: December, 2014

Abstract: Skeletal muscle atrophy is a severe condition of muscle mass loss. Muscle atrophy is caused by a downregulation of protein synthesis and by an increase of protein breakdown due to the ubiquitin-proteasome system and autophagy activation. Upregulat...
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Promoter occupancy of STAT1 in interferon responses is regulated by processive transcription.
Published: December, 2014

Abstract: Interferons regulate immunity by inducing DNA-binding of the transcription factor STAT1 through Y701 phosphorylation. Transcription by STAT1 needs to be restricted to minimize adverse effects of prolonged immune responses. It remains unclear how S...
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The maize brown midrib4 (bm4) gene encodes a functional folylpolyglutamate synthase (FPGS).
Published: December, 2014

Abstract: Mutations in the brown midrib4 (bm4) gene affect the accumulation and composition of lignin in maize. Fine mapping analysis of bm4 narrowed the candidate region to an ~105 kb interval on chromosome 9 containing six genes. Only one of these six gen...
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NFAT Targets Signaling Molecules to Gene Promoters in Pancreatic β Cells.
Published: December, 2014

Abstract: Nuclear factor of activated T cells (NFAT) is activated by calcineurin in response to calcium signals derived by metabolic and inflammatory stress to regulate genes in pancreatic islets. Here we show that NFAT targets MAPKs, p300, and histone deac...
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A Distal Locus Element Mediates IFN-γ Priming of Lipopolysaccharide-Stimulated TNF Gene Expression.
Published: December, 2014

Abstract: Interferon γ (IFN-γ) priming sensitizes monocytes and macrophages to lipopolysaccharide (LPS) stimulation, resulting in augmented expression of a set of genes including TNF. Here, we demonstrate that IFN-γ priming of LPS-stimulated TNF transcripti...
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RB Maintains Quiescence and Prevents Premature Senescence through Upregulation of DNMT1 in Mesenchymal Stromal Cells
Published: December, 2014

Abstract: Many cell therapies currently being tested are based on mesenchymal stromal cells (MSCs). However, MSCs start to enter the senescent state upon long-term expansion. The role of retinoblastoma (RB) protein in regulating MSC properties is not well s...
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Genomic evidence of geographically widespread effect of gene flow from polar bears into brown bears.
Published: December, 2014

Abstract: Polar bears are an arctic, marine adapted species that is closely related to brown bears. Genome analyses have shown that polar bears are distinct and genetically homogeneous in comparison to brown bears. However, these analyses have also revealed...
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Specific but interdependent functions for Arabidopsis AGO4 and AGO6 in RNA-directed DNA methylation.
Published: December, 2014

Abstract: Argonaute (AGO) family proteins are conserved key components of small RNA-induced silencing pathways. In the RNA-directed DNA methylation (RdDM) pathway in Arabidopsis, AGO6 is generally considered to be redundant with AGO4. In this report, our co...
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Initiation of DNA replication from non-canonical sites on an origin-depleted chromosome.
Published: December, 2014

Abstract: Eukaryotic DNA replication initiates from multiple sites on each chromosome called replication origins (origins). In the budding yeast Saccharomyces cerevisiae, origins are defined at discrete sites. Regular spacing and diverse firing characterist...
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CRISPR Reveals a Distal Super-Enhancer Required for Sox2 Expression in Mouse Embryonic Stem Cells.
Published: December, 2014

Abstract: The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency f...
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STAT1-Dependent Signal Integration between IFNγ and TLR4 in Vascular Cells Reflect Pro-Atherogenic Responses in Human Atherosclerosis
Published: December, 2014

Abstract: Signal integration between IFNγ and TLRs in immune cells has been associated with the host defense against pathogens and injury, with a predominant role of STAT1. We hypothesize that STAT1-dependent transcriptional changes in vascular cells involv...
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Retromer vesicles interact with RNA granules in haploid male germ cells.
Published: December, 2014

Abstract: Spermatozoa are produced during spermatogenesis as a result of mitotic proliferation, meiosis and cellular differentiation. Postmeiotic spermatids are exceptional cells given their haploid genome and remarkable sperm-specific structural transforma...
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Environment drives selection and function of enhancers controlling tissue-specific macrophage identities.
Published: December, 2014

Abstract: Macrophages reside in essentially all tissues of the body and play key roles in innate and adaptive immune responses. Distinct populations of tissue macrophages also acquire context-specific functions that are important for normal tissue homeostas...
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Nuclear envelope remodelling during human spermiogenesis involves somatic B-type lamins and a spermatid-specific B3 lamin isoform.
Published: December, 2014

Abstract: The nuclear lamina (NL) is a filamentous protein meshwork, composed essentially of lamins, situated between the inner nuclear membrane and the chromatin. There is mounting evidence that the NL plays a role in spermatid differentiation during sperm...
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The conserved histone deacetylase Rpd3 and its DNA binding subunit Ume6 control dynamic transcript architecture during mitotic growth and meiotic development.
Published: December, 2014

Abstract: It was recently reported that the sizes of many mRNAs change when budding yeast cells exit mitosis and enter the meiotic differentiation pathway. These differences were attributed to length variations of their untranslated regions. The function of...
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Genome-wide DNA methylation analysis in precursor B-cells.
Published: December, 2014

Abstract: DNA methylation is responsible for regulating gene expression and cellular differentiation and for maintaining genomic stability during normal human development. Furthermore, it plays a significant role in the regulation of hematopoiesis. In order...
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Foxk proteins repress the initiation of starvation-induced atrophy and autophagy programs.
Published: December, 2014

Abstract: Autophagy is the primary catabolic process triggered in response to starvation. Although autophagic regulation within the cytosolic compartment is well established, it is becoming clear that nuclear events also regulate the induction or repression...
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Transcription bypass of DNA lesions enhances cell survival but attenuates transcription coupled DNA repair.
Published: December, 2014

Abstract: Transcription-coupled DNA repair (TCR) is a subpathway of nucleotide excision repair (NER) dedicated to rapid removal of DNA lesions in the transcribed strand of actively transcribed genes. The precise nature of the TCR signal and how the repair m...
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RAN-Binding Protein 9 is Involved in Alternative Splicing and is Critical for Male Germ Cell Development and Male Fertility.
Published: December, 2014

Abstract: As a member of the large Ran-binding protein family, Ran-binding protein 9 (RANBP9) has been suggested to play a critical role in diverse cellular functions in somatic cell lineages in vitro, and this is further supported by the neonatal lethality...
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Zinc finger oxidation of Fpg/Nei DNA glycosylases by 2-thioxanthine: biochemical and X-ray structural characterization.
Published: December, 2014

Abstract: DNA glycosylases from the Fpg/Nei structural superfamily are base excision repair enzymes involved in the removal of a wide variety of mutagen and potentially lethal oxidized purines and pyrimidines. Although involved in genome stability, the rece...
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Degradation of DNA damage-independently stalled RNA polymerase II is independent of the E3 ligase Elc1.
Published: December, 2014

Abstract: Transcription elongation is a highly dynamic and discontinuous process, which includes frequent pausing of RNA polymerase II (RNAPII). RNAPII complexes that stall persistently on a gene during transcription elongation block transcription and thus ...
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Evaluation of methods to detect CALR mutations in myeloproliferative neoplasms
Published: November, 2014

Abstract: The recent discovery of somatically acquired CALR mutations in a substantial proportion of patients with myeloproliferative neoplasms has provided a new marker of clonal disease, advancing both diagnosis and prognosis in these previously difficult...
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Natural genetic variation impacts expression levels of coding, non-coding, and antisense transcripts in fission yeast.
Published: November, 2014

Abstract: Our current understanding of how natural genetic variation affects gene expression beyond well-annotated coding genes is still limited. The use of deep sequencing technologies for the study of expression quantitative trait loci (eQTLs) has the pot...
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Regulation of anti-sense transcription by Mot1p and NC2 via removal of TATA-binding protein (TBP) from the 3'-end of genes.
Published: November, 2014

Abstract: The activity and dynamic nature of TATA-binding protein (TBP) crucial to RNA polymerase II-mediated transcription is under control of the Mot1p and NC2 complexes. Here we show that both TBP regulatory factors play 'hidden' roles in ensuring transc...
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Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast.
Published: November, 2014

Abstract: Most long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. Here we focus on a set of intergenic lncRNAs in fission yeast. Deleting one of these lncRNAs exhibited a clear phenotype: drug sensitivity. Detailed analyses...
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Epigenetic memory of the first cell fate decision prevents complete ES cell reprogramming into trophoblast.
Published: November, 2014

Abstract: Embryonic (ES) and trophoblast (TS) stem cells reflect the first, irrevocable cell fate decision in development that is reinforced by distinct epigenetic lineage barriers. Nonetheless, ES cells can seemingly acquire TS-like characteristics upon ma...
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O-GlcNAcylation Prevents Aggregation of the Polycomb Group Repressor Polyhomeotic.
Published: November, 2014

Abstract: The glycosyltransferase Ogt adds O-linked N-Acetylglucosamine (O-GlcNAc) moieties to nuclear and cytosolic proteins. Drosophila embryos lacking Ogt protein arrest development with a remarkably specific Polycomb phenotype, arising from the failure ...
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Cryptogenic stroke and small fiber neuropathy of unknown etiology in patients with alpha-galactosidase A -10T genotype.
Published: November, 2014

Abstract: BackgroundFabry disease (FD) is a multisystemic disorder with typical neurological manifestations such as stroke and small fiber neuropathy (SFN), caused by mutations of the alpha-galactosidase A (GLA) gene. We analyzed 15 patients carrying the GL...
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Synergistic template-free synthesis of dsDNA by Thermococcus nautili primase PolpTN2, DNA polymerase PolB, and pTN2 helicase.
Published: November, 2014

Abstract: A combination of three enzymes from the hyperthermophilic archaeon Thermococcus nautili, DNA primase PolpTN2, DNA polymerase PolB, and pTN2 DNA helicase, was found to synthesize up to 300-400 ng/µl dsDNA from deoxynucleotide triphosphates in less ...
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MiR-98 delays skeletal muscle differentiation by downregulating E2F5.
Published: November, 2014

Abstract: A genome-wide screen had previously shown that knocking down miR-98 and let-7g, two miRNAs of the let-7 family, leads to a dramatic increase of terminal myogenic differentiation. Here we report that a transcriptomic analysis of human myoblasts whe...
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Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway.
Published: November, 2014

Abstract: Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian br...
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Regulatory network decoded from epigenomes of surface ectoderm-derived cell types.
Published: November, 2014

Abstract: Developmental history shapes the epigenome and biological function of differentiated cells. Epigenomic patterns have been broadly attributed to the three embryonic germ layers. Here we investigate how developmental origin influences epigenomes. We...
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Single mutations in sasA enable a simpler ΔcikA gene network architecture with equivalent circadian properties.
Published: November, 2014

Abstract: The circadian input kinase of the cyanobacterium Synechococcus elongatus PCC 7942 (CikA) is important both for synchronizing circadian rhythms with external environmental cycles and for transferring temporal information between the oscillator and ...
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RNA helicase DDX21 coordinates transcription and ribosomal RNA processing.
Published: November, 2014

Abstract: DEAD-box RNA helicases are vital for the regulation of various aspects of the RNA life cycle, but the molecular underpinnings of their involvement, particularly in mammalian cells, remain poorly understood. Here we show that the DEAD-box RNA helic...
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Neuropeptide Y promotes adipogenesis in chicken adipose cells in vitro.
Published: November, 2014

Abstract: Neuropeptide Y is an evolutionarily conserved neurotransmitter that stimulates food intake in higher vertebrate species and promotes adipogenesis in mammals. The objective of this study was to determine if NPY also enhances adipogenesis in birds, ...
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Circadian enhancers coordinate multiple phases of rhythmic gene transcription in vivo.
Published: November, 2014

Abstract: Mammalian transcriptomes display complex circadian rhythms with multiple phases of gene expression that cannot be accounted for by current models of the molecular clock. We have determined the underlying mechanisms by measuring nascent RNA transcr...
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Identification by high-throughput imaging of the histone methyltransferase EHMT2 as an epigenetic regulator of VEGFA alternative splicing.
Published: November, 2014

Abstract: Recent evidence points to a role of chromatin in regulation of alternative pre-mRNA splicing (AS). In order to identify novel chromatin regulators of AS, we screened an RNAi library of chromatin proteins using a cell-based high-throughput in vivo ...
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Global quantitative proteomics reveals novel factors in the ecdysone signaling pathway in Drosophila melanogaster.
Published: November, 2014

Abstract: The ecdysone signaling pathway plays a major role in various developmental transitions in insects. Recent advances in the understanding of ecdysone action have relied to a large extent on the application of molecular genetic tools in Drosophila. H...
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Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence.
Published: November, 2014

Abstract: Hematopoietic stem cell (HSC) specification occurs in the embryonic aorta and requires Notch activation; however, most of the Notch-regulated elements controlling de novo HSC generation are still unknown. Here, we identify putative direct Notch ta...
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Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.
Published: November, 2014

Abstract: Approximately half of poor prognosis neuroblastomas (NBs) are characterized by pathognomonic MYCN gene amplification and MYCN over-expression. Here we present data showing that short-interfering RNA mediated depletion of the protein arginine methy...
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MicroRNAs 206 and 21 Cooperate To Promote RAS-Extracellular Signal-Regulated Kinase Signaling by Suppressing the Translation of RASA1 and SPRED1.
Published: November, 2014

Abstract: Despite the low prevalence of activating point mutation of RAS or RAF genes, the RAS-extracellular signal-regulated kinase (ERK) pathway is implicated in breast cancer pathogenesis. Indeed, in triple-negative breast cancer (TNBC), there is recurre...
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Fission yeast Cactin restricts telomere transcription and elongation by controlling Rap1 levels.
Published: November, 2014

Abstract: The telomeric transcriptome comprises multiple long non-coding RNAs generated by transcription of linear chromosome ends. In a screening performed in Schizosaccharomyces pombe, we identified factors modulating the cellular levels of the telomeric ...
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Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation.
Published: November, 2014

Abstract: Emerging evidence suggests that RANKL-induced changes in chromatin state are important for osteoclastogenesis, but these epigenetic mechanisms are not well understood and have not been therapeutically targeted. In this study, we find that the smal...
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Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals
Published: November, 2014

Abstract: To understand the evolutionary dynamics between transcription factor (TF) binding and gene expression in mammals, we compared transcriptional output and the binding intensities for three tissue-specific TFs in livers from four closely related mous...
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Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes.
Published: November, 2014

Abstract: DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic ac...
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Epigenetic Modification of Histone 3 Lysine 27: Mediator Subunit MED25 is Required for the Dissociation of Polycomb Repressive Complex 2 from the Promoter of Cytochrome P450 2C9.
Published: November, 2014

Abstract: The Mediator complex is vital for the transcriptional regulation of eukaryotic genes. Mediator binds to nuclear receptors at target response elements and recruits chromatin modifying enzymes and RNA Pol II. Here, we examine the involvement of Medi...
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Suppression of the FOXM1 transcriptional programme via novel small molecule inhibition.
Published: November, 2014

Abstract: The transcription factor FOXM1 binds to sequence-specific motifs on DNA (C/TAAACA) through its DNA-binding domain (DBD) and activates proliferation- and differentiation-associated genes. Aberrant overexpression of FOXM1 is a key feature in oncogen...
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HIV-1 Integrase Variants Retarget Viral Integration and Are Associated with Disease Progression in a Chronic Infection Cohort.
Published: November, 2014

Abstract: Distinct integration patterns of different retroviruses, including HIV-1, have puzzled virologists for over 20 years. A tetramer of the viral integrase (IN) assembles on the two viral cDNA ends, docks onto the target DNA (tDNA), and catalyzes vira...
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Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locus Saccharomyces cerevisiae system.
Published: November, 2014

Abstract: Saccharomyces cerevisiae has a complex system for switching the mating type of haploid cells, requiring the genome to have three mating-type (MAT)-like loci and a mechanism for silencing two of them. How this system originated is unknown, because ...
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Heavy transcription of yeast genes correlates with differential loss of histone H2B relative to H4 and queued RNA polymerases.
Published: November, 2014

Abstract: Eukaryotic chromatin is composed of nucleosomes, which contain nearly two coils of DNA wrapped around a central histone octamer. The octamer contains an H3-H4 tetramer and two H2A-H2B dimers. Gene activation is associated with chromatin disruption...
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Serine Deprivation Enhances Anti-neoplastic Activity of Biguanides.
Published: November, 2014

Abstract: Metformin, a biguanide widely used in the treatment of type II diabetes, clearly exhibits anti-neoplastic activity in experimental models and has been reported to reduce cancer incidence in diabetics. . There are ongoing clinical trials to evaluat...
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Combining MeDIP-seq and MRE-seq to investigate genome-wide CpG methylation.
Published: November, 2014

Abstract: DNA CpG methylation is a widespread epigenetic mark in high eukaryotes including mammals. DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and c...
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DNA Copy-Number Control through Inhibition of Replication Fork Progression.
Published: November, 2014

Abstract: Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the lev...
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Silica nanoparticles induce autophagy and endothelial dysfunction via the PI3K/Akt/mTOR signaling pathway.
Published: November, 2014

Abstract: Although nanoparticles have a great potential for biomedical applications, there is still a lack of a correlative safety evaluation on the cardiovascular system. This study is aimed to clarify the biological behavior and influence of silica nanopa...
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The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1.
Published: November, 2014

Abstract: 8-Oxoguanine DNA glycosylase (OGG1), which initiates the repair of DNA purine modifications such as 8-oxo-7,8-dihydroguanine (8-oxoG), is often regarded as a house keeping protein ubiquitously active in mammalian cells. We have analysed the repair...
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A phylogenomic analysis of turtles.
Published: November, 2014

Abstract: Molecular analyses of turtle relationships have overturned prevailing morphological hypotheses and prompted the development of a new taxonomy. Here we provide the first genome-scale analysis of turtle phylogeny. We sequenced 2381 ultraconserved el...
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A variably occupied CTCF binding site in the Ultrabithorax gene in the Drosophila Bithorax Complex.
Published: November, 2014

Abstract: Although the majority of genomic binding sites for the insulator protein CTCF are constitutively occupied, a subset show variably occupancy. Such variable sites provide an opportunity to assess context-specific CTCF functions in gene regulation. H...
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Detection of single nucleotide polymorphisms in Plasmodium falciparum by PCR primer extension and lateral flow immunoassay.
Published: November, 2014

Abstract: Resistance of Plasmodium falciparum to some antimalarial drugs is linked to single nucleotide polymorphisms (SNPs). Currently there are no methods for identification of resistant parasites that are sufficiently simple, cheap and fast to be perform...
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Deregulation of Rb-E2F1 axis causes chromosomal instability by engaging the transactivation function of Cdc20-APC/C complex.
Published: November, 2014

Abstract: E2F family of transcription factors regulate genes involved in various aspects of cell cycle. Beyond the well-documented role in G1/S transition, mitotic regulation by E2F has also been reported. Proper mitotic progression is monitored by spindle ...
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A Novel Mouse Model for the Hyper-IgM Syndrome: A Spontaneous Activation-Induced Cytidine Deaminase Mutation Leading to Complete Loss of Ig Class Switching and Reduced Somatic Hypermutation.
Published: November, 2014

Abstract: We describe a spontaneously derived mouse line that completely failed to induce Ig class switching in vitro and in vivo. The mice inherited abolished IgG serum titers in a recessive manner caused by a spontaneous G→A transition mutation in codon 1...
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Continuous requirement for the TCR in regulatory T cell function.
Published: November, 2014

Abstract: Foxp3(+) regulatory T cells (Treg cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of Tr...
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Blocking of JB6 Cell Transformation by Tanshinone IIA: Epigenetic Reactivation of Nrf2 Antioxidative Stress Pathway.
Published: November, 2014

Abstract: Increasing numbers of natural products have been found to possess anticancer effects. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator of the antioxidative stress response, and our previous studies found that epigenetic mod...
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Characterization of microsatellite markers for pinedrops, Pterospora andromedea (Ericaceae), from Illumina MiSeq sequencing.
Published: November, 2014

Abstract: UNLABELLED: • PREMISE OF THE STUDY: Pterospora andromedea (Ericaceae) is a mycoheterotrophic plant endemic to North America with a disjunct distribution. Eastern populations are in decline compared to western populations. Microsatellite loci will ...
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RNA Processing Factors Swd2.2 and Sen1 Antagonize RNA Pol III-Dependent Transcription and the Localization of Condensin at Pol III Genes.
Published: November, 2014

Abstract: Condensin-mediated chromosome condensation is essential for genome stability upon cell division. Genetic studies have indicated that the association of condensin with chromatin is intimately linked to gene transcription, but what transcription-ass...
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Genome-wide identification of aberrantly methylated promoters in ovarian tissue of prenatally androgenized rats.
Published: November, 2014

Abstract: OBJECTIVE: To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS). DESIGN: Animal model. SETTING: University-affiliated laboratory. ANIMAL(S): Sprague-Dawley rats. INTERVENTION(S)...
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Epstein-Barr virus nuclear antigen 3A protein regulates CDKN2B transcription via interaction with MIZ-1.
Published: November, 2014

Abstract: The Epstein-Barr virus (EBV) nuclear antigen 3 family of protein is critical for the EBV-induced primary B-cell growth transformation process. Using a yeast two-hybrid screen we identified 22 novel cellular partners of the EBNA3s. Most importantly...
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Synthetic secondary chromosomes in Escherichia coli based on the replication origin of chromosome II in Vibrio cholerae.
Published: October, 2014

Abstract: Recent developments in DNA-assembly methods make the synthesis of synthetic chromosomes a reachable goal. However, the redesign of primary chromosomes bears high risks and still requires enormous resources. An alternative approach is the addition ...
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IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism.
Published: October, 2014

Abstract: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder associated with a bone-marrow failure, genome instability, hypersensitivity to DNA crosslinking agents and a predisposition to cancer. Mutations have been documented in 16 FA genes...
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Ultrasensitive proteome analysis using paramagnetic bead technology.
Published: October, 2014

Abstract: In order to obtain a systems-level understanding of a complex biological system, detailed proteome information is essential. Despite great progress in proteomics technologies, thorough interrogation of the proteome from quantity-limited biological...
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Androgen receptor-interacting protein HSPBAP1 facilitates growth of prostate cancer cells in androgen-deficient conditions.
Published: October, 2014

Abstract: Hormonal therapies targeting androgen receptor (AR) are effective in prostate cancer (PCa), but often the cancers progress to fatal castrate-resistant disease. Improved understanding of the cellular events during androgen deprivation would help to...
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Enantioselective regulation of lactate racemization by LarR in Lactobacillus plantarum.
Published: October, 2014

Abstract: Lactobacillus plantarum is a lactic acid bacterium that produces a racemic mixture of L- and D-lactate from sugar fermentation. The inter-conversion of lactate isomers is performed by a lactate racemase (Lar) that is transcriptionally controlled b...
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Loss of Nucleolar Histone Chaperone NPM1 Triggers Rearrangement of Heterochromatin and Synergizes with a Deficiency in DNA Methyltransferase DNMT3A to Drive Ribosomal DNA Transcription.
Published: October, 2014

Abstract: Nucleoli are prominent nuclear structures assembled and organized around actively transcribed ribosomal DNA (rDNA). The nucleolus has emerged as a platform for the organization of chromatin enriched for repressive histone modifications associated ...
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BET bromodomain inhibition suppresses transcriptional responses to cytokine-Jak-STAT signaling in a gene-specific manner in human monocytes.
Published: October, 2014

Abstract: Disruption of the interaction of bromo and extraterminal (BET) proteins with acetylated histones using small molecule inhibitors suppresses Myc-driven cancers and TLR-induced inflammation in mouse models. The predominant mechanism of BET inhibitor...
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Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment
Published: October, 2014

Abstract: The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger pr...
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Epigenetic regulation of inflammatory gene expression in macrophages by selenium.
Published: October, 2014

Abstract: Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of proinflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium suppl...
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AF9 YEATS Domain Links Histone Acetylation to DOT1L-Mediated H3K79 Methylation.
Published: October, 2014

Abstract: The recognition of modified histones by "reader" proteins constitutes a key mechanism regulating gene expression in the chromatin context. Compared with the great variety of readers for histone methylation, few protein modules that recognize histo...
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Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile.
Published: October, 2014

Abstract: The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens. Many antibiotics destroy intestinal microbial communities and increase...
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Next Generation Sequencing Identifies a Novel Rearrangement in the HBB Cluster Permitting to-the-Base Characterization
Published: October, 2014

Abstract: Genetic testing for hemoglobinopathies is required for prenatal diagnosis, understanding complex cases where multiple pathogenic variants may be present or investigating cases of unexplained anemia. Characterization of disease causing variants tha...
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RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells.
Published: October, 2014

Abstract: A fraction of cancer cells maintain telomeres through the telomerase-independent, 'Alternative Lengthening of Telomeres' (ALT) pathway. ALT relies on homologous recombination (HR) between telomeric sequences; yet, what makes ALT telomeres recombin...
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Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation.
Published: October, 2014

Abstract: Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic...
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The miR-155-PU.1 axis acts on Pax5 to enable efficient terminal B cell differentiation.
Published: October, 2014

Abstract: A single microRNA (miRNA) can regulate the expression of many genes, though the level of repression imparted on any given target is generally low. How then is the selective pressure for a single miRNA/target interaction maintained across long evol...
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Biogeochemical Typing of Paddy Field by a Data-Driven Approach Revealing Sub-Systems within a Complex Environment - A Pipeline to Filtrate, Organize and Frame Massive Dataset from Multi-Omics Analyses.
Published: October, 2014

Abstract: We propose the technique of biogeochemical typing (BGC typing) as a novel methodology to set forth the sub-systems of organismal communities associated to the correlated chemical profiles working within a larger complex environment. Given the intr...
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In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9.
Published: October, 2014

Abstract: Probing gene function in the mammalian brain can be greatly assisted with methods to manipulate the genome of neurons in vivo. The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococc...
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Transforming Growth Factor β1 (TGF-β1) Enhances Expression of Profibrotic Genes through a Novel Signaling Cascade and MicroRNAs in Renal Mesangial Cells.
Published: October, 2014

Abstract: Increased expression of transforming growth factor-β1 (TGF-β1) in glomerular mesangial cells (MC) augments extracellular matrix accumulation and hypertrophy during the progression of diabetic nephropathy (DN), a debilitating renal complication of ...
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A nanobody modulates the p53 transcriptional program without perturbing its functional architecture.
Published: October, 2014

Abstract: The p53 transcription factor plays an important role in genome integrity. To perform this task, p53 regulates the transcription of genes promoting various cellular outcomes including cell cycle arrest, apoptosis or senescence. The precise regulati...
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Drosophila oncogene Gas41 is RNAi modulator that intersects heterochromatin and siRNA pathway.
Published: October, 2014

Abstract: Glioma amplified sequence41 (Gas41) is a highly conserved putative transcription factor that is frequently abundant in human gliomas. Gas41 shows oncogenic activity by promoting cell growth and viability. Here we show Gas41 is required for proper ...
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KDM5 Interacts with Foxo to Modulate Cellular Levels of Oxidative Stress
Published: October, 2014

Abstract: Increased cellular levels of oxidative stress are implicated in a large number of human diseases. Here we describe the transcription co-factor KDM5 (also known as Lid) as a new critical regulator of cellular redox state. Moreover, this occurs thro...
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Sperm DNA Methylation Analysis in Swine Reveals Conserved and Species-Specific Methylation Patterns and Highlights an Altered Methylation at the GNAS Locus in Infertile Boars.
Published: October, 2014

Abstract: Male infertility is an increasing health issue in today's society, for both human or livestock populations. In livestock, male infertility slows the improvement of animal selection programs and agricultural productivity. There are increasing evide...
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Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity.
Published: October, 2014

Abstract: Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene e...
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Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Published: October, 2014

Abstract: Naive embryonic stem cells hold great promise for research and therapeutics as they have broad and robust developmental potential. While such cells are readily derived from mouse blastocysts it has not been possible to isolate human equivalents ea...
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ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers.
Published: October, 2014

Abstract: Aggressive neuroendocrine lung cancers, including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), represent an understudied tumor subset that accounts for approximately 40,000 new lung cancer cases per year in the United Stat...
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Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7.
Published: October, 2014

Abstract: What causes the tissue-specific pathology of diseases resulting from mutations in housekeeping genes? Specifically, in spinocerebellar ataxia type 7 (SCA7), a neurodegenerative disorder caused by a CAG-repeat expansion in ATXN7 (which encodes an e...
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MeDIP-on-Chip for Methylation Profiling
Published: October, 2014

Abstract: DNA methylation is an important regulatory step in gene expression. Knowledge of the alterations in DNA methylation at a whole genome scale improves our understanding of gene regulation and potential correlations with biological events or disease ...
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Chromatin features of plant telomeric sequences at terminal versus internal positions
Published: October, 2014

Abstract: Epigenetic mechanisms are involved in regulation of crucial cellular processes in eukaryotic organisms. Data on the epigenetic features of plant telomeres and their epigenetic regulation were published mostly for Arabidopsis thaliana, in which the...
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Inactivation of Phaeodactylum tricornutum urease gene using transcription activator-like effector nuclease-based targeted mutagenesis.
Published: October, 2014

Abstract: Diatoms are unicellular photosynthetic algae with promise for green production of fuels and other chemicals. Recent genome-editing techniques have greatly improved the potential of many eukaryotic genetic systems, including diatoms, to enable know...
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Notch signaling regulates myogenic regenerative capacity of murine and human mesoangioblasts.
Published: October, 2014

Abstract: Somatic stem cells hold attractive potential for the treatment of muscular dystrophies (MDs). Mesoangioblasts (MABs) constitute a myogenic subset of muscle pericytes and have been shown to efficiently regenerate dystrophic muscles in mice and dogs...
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HDAC6-ubiquitin interaction controls the duration of HSF1 activation after heat-shock.
Published: October, 2014

Abstract: After heat-shock, HSF1 controls a major cellular transcriptional response involving the activation of early (Hsp70) and late (Hsp25) heat shock gene expression. Here we show that a full response to heat shock (activation of both Hsp70 and Hsp25) d...
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cAMP Responsive Element Binding Protein (CREB) and cAMP Co-regulate Activator Protein 1 (AP1)-Dependent Regeneration-Associated Gene Expression and Neurite Growth.
Published: October, 2014

Abstract: To regenerate damaged axons, neurons must express a cassette of regeneration-associated genes (RAGs) that increases intrinsic growth capacity and confers resistance to extrinsic inhibitory cues. Here we show that dibutyrl-cAMP or forskolin combine...
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ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells.
Published: October, 2014

Abstract: The RAS/ERK pathway is commonly activated in carcinomas and promotes oncogenesis by altering transcriptional programs. However, the array of cis-regulatory elements and trans-acting factors that mediate these transcriptional changes is still uncle...
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Cellular uptake behaviour, photothermal therapy performance, and cytotoxicity of gold nanorods with various coatings.
Published: October, 2014

Abstract: With the development of Au nanorods for a number of biomedical applications, understanding their cellular responses has become increasingly important. In this study, we systematically evaluated the cellular uptake behaviour and cytotoxicity of Au ...
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The Polycomb Group Gene EMF2B is essential for maintenance of floral meristem determinacy in rice.
Published: October, 2014

Abstract: The Polycomb Repressive Complex 2 (PRC2) represses transcriptional activity of target genes through trimethylation of Lysine 27 of Histone H3. The functions of the plant PRC2 have been chiefly described in Arabidopsis but specific functions in oth...
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Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver
Published: October, 2014

Abstract: Obesity contributes to the development of non‑alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; als...
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Altered promoter nucleosome positioning is an early event in gene silencing.
Published: October, 2014

Abstract: Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DN...
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SOX11 promotes tumor angiogenesis through transcriptional regulation of PDGFA in mantle cell lymphoma.
Published: October, 2014

Abstract: SOX11 is overexpressed in several solid tumors and in the vast majority of aggressive mantle cell lymphomas (MCLs). We have recently proven that SOX11 silencing reduces tumor growth in a MCL xenograft model, consistent with the indolent clinical c...
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Integrator Regulates Transcriptional Initiation and Pause Release following Activation.
Published: October, 2014

Abstract: In unicellular organisms, initiation is the rate-limiting step in transcription; in metazoan organisms, the transition from initiation to productive elongation is also important. Here, we show that the RNA polymerase II (RNAPII)-associated multipr...
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Predicting interactome networks perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia.
Published: October, 2014

Abstract: Genomic variations such as point mutations and gene fusions are directly or indirectly associated with human diseases. They are recognized as diagnostic, prognostic markers and therapeutic targets. However, predicting the functional impact of thes...
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Hairy root transformation using Agrobacterium rhizogenes as a tool for exploring cell type-specific gene expression and function using tomato as a model.
Published: October, 2014

Abstract: Agrobacterium rhizogenes (or Rhizobium rhizogenes) is able to transform plant genomes and induce the production of hairy roots. We describe the use of A. rhizogenes in tomato (Solanum spp.) to rapidly assess gene expression and function. Gene expr...
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The PML-associated protein DEK regulates the balance of H3.3 loading on chromatin and is important for telomere integrity.
Published: October, 2014

Abstract: Histone variant H3.3 is deposited in chromatin at active sites, telomeres, and pericentric heterochromatin by distinct chaperones, but the mechanisms of regulation and coordination of chaperone-mediated H3.3 loading remain largely unknown. We show...
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Epigenetic mechanisms regulate placental c-myc and hTERT in normal and pathological pregnancies; c-myc as a novel fetal DNA epigenetic marker for pre-eclampsia.
Published: October, 2014

Abstract: Placental development is known for its resemblance with tumor development, such as in the expression of oncogenes (c-myc) and telomerase (hTERT). The expression of c-myc and hTERT is up-regulated during early pregnancy and gestational trophoblasti...
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A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia.
Published: October, 2014

Abstract: Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new...
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Head formation: OTX2 regulates Dkk1 and Lhx1 activity in the anterior mesendoderm.
Published: October, 2014

Abstract: The Otx2 gene encodes a paired-type homeobox transcription factor that is essential for the induction and the patterning of the anterior structures in the mouse embryo. Otx2 knockout embryos fail to form a head. Whereas previous studies have shown...
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Genome-wide mapping of yeast histone chaperone anti-silencing function 1 reveals its role in condensin binding with chromatin.
Published: September, 2014

Abstract: Genome-wide participation and importance of the histone chaperone Asf1 (Anti-Silencing Function 1) in diverse DNA transactions like replication, repair, heterochromatic silencing and transcription are well documented. Yet its genome-wide targets h...
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c-Rel Regulates Ezh2 Expression in Activated Lymphocytes and Malignant Lymphoid Cells.
Published: September, 2014

Abstract: The Polycomb group protein Ezh2 is a histone methyltransferase that modifies chromatin structure to alter gene expression during embryonic development, lymphocyte activation and tumorigenesis. The mechanism by which Ezh2 expression is regulated is...
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Co-regulated expression of Na+/phosphate Pho89 transporter and Ena1 Na+-ATPase allows their functional coupling under high pH stress.
Published: September, 2014

Abstract: The yeast Saccharomyces cerevisiae has two main high-affinity inorganic phosphate (Pi) transporters, Pho84 and Pho89, functionally relevant at acidic/neutral pH and alkaline pH, respectively. Upon Pi starvation PHO84 and PHO89 are induced by activ...
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Retrotransposon-based profiling of mammalian epigenomes: DNA methylation of IAP LTRs in embryonic stem, somatic and cancer cells.
Published: September, 2014

Abstract: In the current study, we have used HT-TREBS to individually analyze the DNA methylation pattern of 4799 IAP LTR retrotransposons in embryonic stem, somatic and Neuro2A cells. According to the results, half of the loci within this family show const...
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An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons.
Published: September, 2014

Abstract: Throughout evolution primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, ...
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Co-detection and sequencing of genes and transcripts from the same single cells facilitated by a microfluidics platform.
Published: September, 2014

Abstract: Despite the recent advance of single-cell gene expression analyses, co-measurement of both genomic and transcriptional signatures at the single-cell level has not been realized. However such analysis is necessary in order to accurately delineate h...
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Significance of glioma-associated oncogene homolog 1 (GLI1) expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF¿B) pathway.
Published: September, 2014

Abstract: IntroductionThe recently identified claudin-low subtype of breast cancer is enriched for cells with stem-like and mesenchymal-like characteristics. This subtype is most often triple-negative (lacking the estrogen and progesterone receptors (ER, PR...
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Vitamin d receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.
Published: September, 2014

Abstract: The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe ...
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Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression.
Published: September, 2014

Abstract: Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain ...
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5mC Oxidation by Tet2 Modulates Enhancer Activity and Timing of Transcriptome Reprogramming during Differentiation.
Published: September, 2014

Abstract: In mammals, cytosine methylation (5mC) is widely distributed throughout the genome but is notably depleted from active promoters and enhancers. While the role of DNA methylation in promoter silencing has been well documented, the function of this ...
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Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation.
Published: September, 2014

Abstract: GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute geno...
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Asparagine synthetase deficiency detected by whole exome sequencing causes congenital microcephaly, epileptic encephalopathy and psychomotor delay.
Published: September, 2014

Abstract: Deficiency of Asparagine Synthetase (ASNSD, MIM 615574) is a very rare autosomal recessive disorder presenting with some brain abnormalities. Affected individuals have congenital microcephaly and progressive encephalopathy associated with severe i...
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Measuring fast gene dynamics in single cells with timelapse luminescence microscopy
Published: September, 2014

Abstract: Timelapse fluorescence microscopy is an important tool for measuring in vivo gene dynamics in single cells. However, fluorescent proteins are limited by slow chromophore maturation times and the cellular auto-fluorescence or photo-toxicity that ar...
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Genome-wide map of regulatory interactions in the human genome.
Published: September, 2014

Abstract: Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, G...
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SNAIL1 combines competitive displacement of ASCL2 and epigenetic mechanisms to rapidly silence the EPHB3 tumor suppressor in colorectal cancer.
Published: September, 2014

Abstract: EPHB3 is a critical cellular guidance factor in the intestinal epithelium and an important tumor suppressor in colorectal cancer (CRC) whose expression is frequently lost at the adenoma-carcinoma transition when tumor cells become invasive. The mo...
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Genome-wide CNV analysis in 221 unrelated patients and targeted high-throughput sequencing reveal novel causative candidate genes for colorectal adenomatous polyposis.
Published: September, 2014

Abstract: To uncover novel causative genes in patients with unexplained adenomatous polyposis, a model disease for colorectal cancer, we performed a genome-wide analysis of germline copy number variants (CNV) in a large, well characterized APC and MUTYH mut...
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6-methoxyflavone inhibits NFAT translocation into the nucleus and suppresses T cell activation.
Published: September, 2014

Abstract: NFAT plays a crucial role in the immune system by regulating the transcription of inducible genes during immune responses. In T cells, NFAT proteins govern various cellular events related to T cell development, activation, tolerance induction, and...
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TELP, a sensitive and versatile library construction method for next-generation sequencing.
Published: September, 2014

Abstract: Next-generation sequencing has been widely used for the genome-wide profiling of histone modifications, transcription factor binding and gene expression through chromatin immunoprecipitated DNA sequencing (ChIP-seq) and cDNA sequencing (RNA-seq). ...
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Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers.
Published: September, 2014

Abstract: The transcription activator-like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR) associated protein (Cas9) utlilize distinct molecular mechanisms in targeting site recognition. The two protein...
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Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF.
Published: September, 2014

Abstract: HP1 proteins are transcriptional regulators that, like histones, are targets for post-translational modifications defining an HP1-mediated subcode. HP1γ has multiple phosphorylation sites, including serine 83 (S83) that marks it to sites of active...
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The DEK oncoprotein binds to highly and ubiquitously expressed genes with a dual role in their transcriptional regulation.
Published: September, 2014

Abstract: BACKGROUND: The DEK gene is highly expressed in a wide range of cancer cells, and a recurrent translocation partner in acute myeloid leukemia. While DEK has been identified as one of the most abundant proteins in human chromatin, its function and ...
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Up to date sample preparation of proteins for mass spectrometric analysis.
Published: September, 2014

Abstract: Abstract For the identification of proteins from biological samples by mass spectrometry there are two scenarios. Proteins are pre-fractionated in some way or are analysed as a complex mixture (shotgun). Shotgun proteomics recently became more pop...
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Target enrichment of ultraconserved elements from arthropods provides a genomic perspective on relationships among Hymenoptera.
Published: September, 2014

Abstract: Gaining a genomic perspective on phylogeny requires the collection of data from many putatively independent loci across the genome. Among insects, an increasingly common approach to collecting this class of data involves transcriptome sequencing, ...
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Neural stem cell differentiation is dictated by distinct actions of nuclear receptor corepressors and histone deacetylases.
Published: September, 2014

Abstract: Signaling factors including retinoic acid (RA) and thyroid hormone (T3) promote neuronal, oligodendrocyte, and astrocyte differentiation of cortical neural stem cells (NSCs). However, the functional specificity of transcriptional repressor checkpo...
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NKCC1 mediates traumatic brain injury-induced hippocampal neurogenesis through CREB phosphorylation and HIF-1α expression.
Published: September, 2014

Abstract: Traumatic brain injury (TBI) is one of the most prevalent causes of worldwide mortality and morbidity. We previously had evidenced that TBI induced Na-K-2Cl co-transporter (NKCC1) upregulation in hippocampus. Here, we aim to investigate the role o...
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PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.
Published: September, 2014

Abstract: The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorde...
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PaperClip: rapid multi-part DNA assembly from existing libraries.
Published: September, 2014

Abstract: Assembly of DNA 'parts' to create larger constructs is an essential enabling technique for bioengineering and synthetic biology. Here we describe a simple method, PaperClip, which allows flexible assembly of multiple DNA parts from currently exist...
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Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours.
Published: September, 2014

Abstract: Wilms tumour is the most common childhood kidney cancer. Here we report the whole-exome sequencing of 44 Wilms tumours, identifying missense mutations in the microRNA (miRNA)-processing enzymes DROSHA and DICER1, and novel mutations in MYCN, SMARC...
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The pro-apoptotic activity of Drosophila Rbf1 involves dE2F2-dependent downregulation of diap1 and buffy mRNA.
Published: September, 2014

Abstract: The retinoblastoma gene, rb, ensures at least its tumor suppressor function by inhibiting cell proliferation. Its role in apoptosis is more complex and less described than its role in cell cycle regulation. Rbf1, the Drosophila homolog of Rb, has ...
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Identification of a Face Enhancer Reveals Direct Regulation of LIM homeobox 8 (Lhx8) by Wingless-Int (WNT)/β-catenin Signaling.
Published: September, 2014

Abstract: Development of the mammalian face requires a large number of genes that are expressed with spatio-temporal specificity, and transcriptional regulation mediated by enhancers plays a key role in the precise control of gene expression. Using chromati...
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Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation.
Published: September, 2014

Abstract: Overexpression of the histone methyltransferase MMSET in t(4;14)+ multiple myeloma patients is believed to be the driving factor in the pathogenesis of this subtype of myeloma. MMSET catalyzes dimethylation of lysine 36 on histone H3 (H3K36me2), a...
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Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors.
Published: September, 2014

Abstract: Cell type-specific master transcription factors (TFs) play vital roles in defining cell identity and function. However, the roles ubiquitous factors play in the specification of cell identity remain underappreciated. Here we show that the ubiquito...
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Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells.
Published: September, 2014

Abstract: REV1-deficient chicken DT40 cells are compromised in replicating G quadruplex (G4)-forming DNA. This results in localised, stochastic loss of parental chromatin marks and changes in gene expression. We previously proposed that this epigenetic inst...
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Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms.
Published: September, 2014

Abstract: In addition to its well-characterized role in the regulation of drug metabolism and transport by xenobiotics, pregnane X receptor (PXR) critically impacts on lipid homeostasis. In mice, both ligand-dependent activation and knockout of PXR were pre...
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A dynamic CTCF chromatin binding landscape promotes DNA hydroxymethylation and transcriptional induction of adipocyte differentiation.
Published: September, 2014

Abstract: CCCTC-binding factor (CTCF) is a ubiquitously expressed multifunctional transcription factor characterized by chromatin binding patterns often described as largely invariant. In this context, how CTCF chromatin recruitment and functionalities are ...
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Mechanism-based genotoxicity screening of metal oxide nanoparticles using the ToxTracker panel of reporter cell lines.
Published: September, 2014

Abstract: BACKGROUND: The rapid expansion of manufacturing and use of nano-sized materials fuels the demand for fast and reliable assays to identify their potential hazardous properties and underlying mechanisms. The ToxTracker assay is a recently developed...
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Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes.
Published: September, 2014

Abstract: The autism susceptibility candidate 2 gene (AUTS2) has been associated with multiple neurological diseases including autism spectrum disorders (ASDs). Previous studies showed that AUTS2 has an important neurodevelopmental function and is a suspect...
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Highly conserved ENY2/Sus1 protein binds to Drosophila CTCF and is required for barrier activity.
Published: September, 2014

Abstract: Chromatin insulators affect interactions between promoters and enhancers/silencers and function as barriers for the spreading of repressive chromatin. Drosophila insulator protein dCTCF marks active promoters and boundaries of many histone H3K27 t...
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A thermo-halo-tolerant and proteinase-resistant endoxylanase from Bacillus sp. HJ14.
Published: September, 2014

Abstract: A glycosyl hydrolase family 10 endoxylanase from Bacillus sp. HJ14 was grouped in a separated cluster with another six Bacillus endoxylanases which have not been characterized. These Bacillus endoxylanases showed less than 52% amino acid sequence ...
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Nanog induces hyperplasia without initiating tumors.
Published: September, 2014

Abstract: Though expression of the homeobox transcription factor Nanog is generally restricted to pluripotent cells and early germ cells, many contradictory reports about Nanog's involvement in tumorigenesis exist. To address this, a modified Tet-On system ...
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Chromatin enrichment for proteomics.
Published: September, 2014

Abstract: During interphase, chromatin hosts fundamental cellular processes, such as gene expression, DNA replication and DNA damage repair. To analyze chromatin on a proteomic scale, we have developed chromatin enrichment for proteomics (ChEP), which is a ...
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Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development.
Published: September, 2014

Abstract: Cardiac development arises from two sources of mesoderm progenitors, the first heart field (FHF) and the second (SHF). Mesp1 has been proposed to mark the most primitive multipotent cardiac progenitors common for both heart fields. Here, using clo...
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Hypomethylated pollen bypasses the interploidy hybridization barrier in Arabidopsis.
Published: September, 2014

Abstract: Plants of different ploidy levels are separated by a strong postzygotic hybridization barrier that is established in the endosperm. Deregulated parent-of-origin specific genes cause the response to interploidy hybridizations, revealing an epigenet...
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Transgenic analysis of the Leishmania MAP kinase MPK10 reveals an auto-inhibitory mechanism crucial for stage-regulated activity and parasite viability.
Published: September, 2014

Abstract: Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection. The signaling mechanisms underlying p...
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Dopamine signaling leads to loss of polycomb repression and aberrant gene activation in experimental parkinsonism.
Published: September, 2014

Abstract: Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3...
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Y chromosomes of 40% Chinese descend from three Neolithic super-grandfathers.
Published: August, 2014

Abstract: Demographic change of human populations is one of the central questions for delving into the past of human beings. To identify major population expansions related to male lineages, we sequenced 78 East Asian Y chromosomes at 3.9 Mbp of the non-rec...
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oxBS-450K: A method for analysing hydroxymethylation using 450K BeadChips.
Published: August, 2014

Abstract: DNA methylation analysis has become an integral part of biomedical research. For high-throughput applications such as epigenome-wide association studies, the Infinium HumanMethylation450 (450K) BeadChip is currently the platform of choice. However...
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Differences among brain tumor stem cell types and fetal neural stem cells in focal regions of histone modifications and DNA methylation, broad regions of modifications, and bivalent promoters.
Published: August, 2014

Abstract: BACKGROUND: Aberrational epigenetic marks are believed to play a major role in establishing the abnormal features of cancer cells. Rational use and development of drugs aimed at epigenetic processes requires an understanding of the range, extent, ...
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Mediator can regulate mitotic entry and direct periodic transcription in fission yeast.
Published: August, 2014

Abstract: Cdk8 is required for correct timing of mitotic progression in fission yeast. How the activity of Cdk8 is regulated is unclear, since the kinase is not activated by T-loop phosphorylation and its partner CycC, does not oscillate. Cdk8 is however a ...
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Histone methylation has distinct dynamics from histone acetylation in cell cycle re-entry from quiescence.
Published: August, 2014

Abstract: Cell growth is attuned to nutrient availability to sustain homeostatic biosynthetic processes. In unfavorable environments, cells enter a non-proliferative state termed quiescence, but rapidly return to the cell cycle once conditions support energ...
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Immunogenetics. Chromatin state dynamics during blood formation.
Published: August, 2014

Abstract: Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics; however, technical limitations impede profiling of...
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Interferon γ-inducible protein (IFI) 16 transcriptionally regulates type i interferons and other interferon-stimulated genes and controls the interferon response to both DNA and RNA viruses.
Published: August, 2014

Abstract: The interferon γ-inducible protein 16 (IFI16) has recently been linked to the detection of nuclear and cytosolic DNA during infection with herpes simplex virus-1 and HIV. IFI16 binds dsDNA via HIN200 domains and activates stimulator of interferon ...
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The ROS-sensitive microRNA-9/9* controls the expression of mitochondrial tRNA-modifying enzymes and is involved in the molecular mechanism of MELAS syndrome.
Published: August, 2014

Abstract: Mitochondrial dysfunction activates mitochondria-to-nucleus signaling pathways whose components are mostly unknown. Identification of these components is important to understand the molecular mechanisms underlying mitochondrial diseases and to dis...
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Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming.
Published: August, 2014

Abstract: Nuclear transfer to oocytes is an efficient way to transcriptionally reprogram somatic nuclei, but its mechanisms remain unclear. Here, we identify a sequence of molecular events that leads to rapid transcriptional reprogramming of somatic nuclei ...
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A Macrohistone Variant Links Dynamic Chromatin Compaction to BRCA1-Dependent Genome Maintenance.
Published: August, 2014

Abstract: Appropriate DNA double-strand break (DSB) repair factor choice is essential for ensuring accurate repair outcome and genomic integrity. The factors that regulate this process remain poorly understood. Here, we identify two repressive chromatin com...
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Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death.
Published: August, 2014

Abstract: Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented, but the mechanism underlying this process is poorly unders...
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Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1.
Published: August, 2014

Abstract: Haematopoietic stem cells (HSCs) are self-renewing stem cells capable of replenishing all blood lineages. In all vertebrate embryos that have been studied, definitive HSCs are generated initially within the dorsal aorta (DA) of the embryonic vascu...
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Polycomb Protein EED is Required for Silencing of Pluripotency Genes upon ESC Differentiation.
Published: August, 2014

Abstract: Eed (embryonic ectoderm development) is a core component of the Polycomb Repressive Complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27). Trimethylated H3K27 (H3K27me3) can act as a signal for PRC1 recruitment in the pr...
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Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia.
Published: August, 2014

Abstract: T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the functio...
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The unfolded protein response and the phosphorylations of activating transcription factor 2 in the trans-activation of il23a produced by β-glucans.
Published: August, 2014

Abstract: Current views on the control of IL-23 production focus on the regulation of il23a, the gene encoding IL-23 p19, by NF-κB in combination with other transcription factors. CHOP, XBP1, AP1, SMAD, C/EBPβ, and CREB have been involved in response to LPS...
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Insights into the epigenomic landscape of the human malaria vector Anopheles gambiae.
Published: August, 2014

Abstract: The epigenome of the human malaria vector Anopheles gambiae was characterized in midgut cells by mapping the distribution and levels of two post-translational histone modifications, H3K27ac and H3K27me3. These histone profiles were then correlated...
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KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress.
Published: August, 2014

Abstract: During the recent years lysine methyltransferase Set7/9 ((Su(var)-3-9, Enhancer-of-Zeste, Trithorax) domain containing protein 7/9) has emerged as an important regulator of different transcription factors. In this study, we report a novel function...
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Temporospatial Coordination of Meiotic DNA Replication and Recombination via DDK Recruitment to Replisomes.
Published: August, 2014

Abstract: It has been long appreciated that, during meiosis, DNA replication is coordinated with the subsequent formation of the double-strand breaks (DSBs) that initiate recombination, but a mechanistic understanding of this process was elusive. We now sho...
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An improved method for including upper size range plasmids in metamobilomes.
Published: August, 2014

Abstract: Two recently developed isolation methods have shown promise when recovering pure community plasmid DNA (metamobilomes/plasmidomes), which is useful in conducting culture-independent investigations into plasmid ecology. However, both methods employ...
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Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new mithramycin analogue.
Published: August, 2014

Abstract: Ovarian cancer has a poor prognosis due to intrinsic or acquired resistance to some cytotoxic drugs, raising the interest in new DNA-binding agents such as mithramycin analogues as potential chemotherapeutic agents in gynecological cancer. Using a...
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A long noncoding RNA protects the heart from pathological hypertrophy.
Published: August, 2014

Abstract: The role of long noncoding RNA (lncRNA) in adult hearts is unknown; also unclear is how lncRNA modulates nucleosome remodelling. An estimated 70% of mouse genes undergo antisense transcription, including myosin heavy chain 7 (Myh7), which encodes ...
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Dynamics of carbon concentrating mechanism induction and protein re-localisation during the dark to light transition in synchronised Chlamydomonas.
Published: August, 2014

Abstract: In the model green alga Chlamydomonas reinhardtii, a carbon concentrating mechanism (CCM) is induced under low CO2 in the light and comprises: active inorganic carbon transport components, carbonic anhydrases and aggregation of Rubisco in the chlo...
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Identification and Validation of Genetic Variants that Influence Transcription Factor and Cell Signaling Protein Levels.
Published: August, 2014

Abstract: Many genetic variants associated with human disease have been found to be associated with alterations in mRNA expression. Although it is commonly assumed that mRNA expression changes will lead to consequent changes in protein levels, methodologica...
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eQTL Mapping of Transposon Silencing Reveals a Position-Dependent Stable Escape from Epigenetic Silencing and Transposition of AtMu1 in the Arabidopsis Lineage.
Published: August, 2014

Abstract: Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a small...
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Inappropriate p53 activation during development induces features of CHARGE syndrome.
Published: August, 2014

Abstract: CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Desp...
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Whole Exome Sequencing for Familial Bicuspid Aortic Valve Identifies Putative Variants.
Published: August, 2014

Abstract: BACKGROUND: -Bicuspid aortic valve (BAV) is the most common congenital cardiovascular malformation (CVM). Although highly heritable, few causal variants have been identified. The purpose of this study was to identify genetic variants underlying B...
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Genetic variants within the second intron of the KCNQ1 gene affect CTCF binding and confer a risk of Beckwith-Wiedemann syndrome upon maternal transmission.
Published: August, 2014

Abstract: BACKGROUND: Disruption of 11p15 imprinting results in two fetal growth disorders with opposite phenotypes: the Beckwith-Wiedemann (BWS; MIM 130650) and the Silver-Russell (SRS; MIM 180860) syndromes. DNA methylation defects account for 60% of BWS ...
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Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3.
Published: August, 2014

Abstract: Insulinoma associated 1 (Insm1) plays an important role in regulating the development of cells in the central and peripheral nervous systems, olfactory epithelium and endocrine pancreas. To better define the role of Insm1 in pancreatic endocrine c...
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Cell isolation induces fate changes of bone marrow mesenchymal cells leading to loss or alternatively to acquisition of new differentiation potentials.
Published: August, 2014

Abstract: Mesenchymal stromal cell populations include a fraction, termed mesenchymal stem cells, exhibiting multipotency. Other cells within this population possess a lesser differentiation range. This was assumed to be due to a mesenchymal cellular cascad...
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Active CREB1 Promotes a Malignant TGFβ2 Autocrine Loop in Glioblastoma.
Published: August, 2014

Abstract: In advanced cancer, including glioblastoma, the TGFβ pathway acts as an oncogenic factor. Some tumors exhibit aberrantly high TGFβ activity, and the mechanisms underlying this phenomenon are not well understood. We have observed that TGFβ can indu...
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Human cytomegalovirus pUL79 is an elongation factor of RNA polymerase II for viral gene transcription.
Published: August, 2014

Abstract: In this study, we have identified a unique mechanism in which human cytomegalovirus (HCMV) protein pUL79 acts as an elongation factor to direct cellular RNA polymerase II for viral transcription during late times of infection. We and others previo...
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Regulation of broad by the Notch pathway affects timing of follicle cell development.
Published: August, 2014

Abstract: During Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets ...
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Source tracking of an anthrax outbreak in northeastern China using complete genome analysis and MLVA genotyping.
Published: July, 2014

Abstract: Anthrax is caused by Bacillus anthracis, an etiological agent behind zoonotic diseases worldwide. B. anthracis is also one of the most dangerous bioterrorism agents. An anthrax outbreak took place in Liaoning Province in northeastern China in Augu...
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Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment.
Published: July, 2014

Abstract: BACKGROUND: H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the ...
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SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma.
Published: July, 2014

Abstract: Although the principles that balance stem cell self-renewal and differentiation in normal tissue homeostasis are beginning to emerge, it is still unclear whether cancer cells with tumour initiating potential are similarly governed, or whether they...
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Lipid peroxidation product 4-hydroxy-2-nonenal modulates base excision repair in human cells.
Published: July, 2014

Abstract: Oxidative-stress-driven lipid peroxidation (LPO) is involved in the pathogenesis of several human diseases, including cancer. LPO products react with cellular proteins changing their properties, and with DNA bases to form mutagenic etheno-DNA addu...
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Interlocked loops trigger lineage specification and stable fates in the Drosophila nervous system.
Published: July, 2014

Abstract: Multipotent precursors are plastic cells that generate different, stable fates at the correct number, place and time, to allow tissue and organ formation. While fate determinants are known to trigger specific transcriptional programs, the molecula...
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Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model.
Published: July, 2014

Abstract: Although great advances have been made in the treatment of pediatric acute lymphoblastic leukemia, up to one of five patients will relapse, and their prognosis thereafter is dismal. We have previously identified recurrent deletions in TBL1XR1, whi...
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Histone deacetylase 4 promotes ubiquitin-dependent proteasomal degradation of Sp3 in SH-SY5Y cells treated with di(2-ethylhexyl)phthalate (DEHP), determining neuronal death.
Published: July, 2014

Abstract: Phthalates, phthalic acid esters, are widely used as plasticizers to produce polymeric materials in industrial production of plastics and daily consumable products. Animal studies have shown that di(2-ethylhexyl)phthalate (DEHP) may cause toxic ef...
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H19 and MEST gene expression and histone modification in blastocysts cultured from vitrified and fresh two-cell mouse embryos
Published: July, 2014

Abstract: Vitrification of embryos is a routine procedure in many IVF laboratories. The effect of vitrification on gene expression and some modifications of H3 histone in H19 and MEST imprinted genes in blastocysts produced in vitro from non-vitrified and v...
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AhR and Arnt differentially regulate NF-κB signaling and chemokine responses in human bronchial epithelial cells.
Published: July, 2014

Abstract: BACKGROUND: The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of...
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Concerted activities of distinct H4K20 methyltransferases at DNA double-strand breaks regulate 53BP1 nucleation and NHEJ-directed repair.
Published: July, 2014

Abstract: Although selective binding of 53BP1 to dimethylated histone H4 lysine 20 (H4K20me2) at DNA double-strand breaks (DSBs) is a necessary and pivotal determinant of nonhomologous end joining (NHEJ)-directed repair, the enzymes that generate H4K20me2 a...
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DNA Break Mapping Reveals Topoisomerase II Activity Genome-Wide.
Published: July, 2014

Abstract: Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand...
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Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy.
Published: July, 2014

Abstract: We assessed a large consanguineous Pakistani family (PKAB157) segregating early onset low vision problems. Funduscopic and electroretinographic evaluation of affected individuals revealed juvenile cone-rod dystrophy (CRD) with maculopathy. Other c...
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Genome-Wide Characterization of Light-Regulated Genes in Neurospora crassa.
Published: July, 2014

Abstract: The filamentous fungus Neurospora crassa responds to light in complex ways. To thoroughly study the transcriptional response of this organism to light, RNA-seq was used to analyze capped and polyadenylated mRNA prepared from mycelium grown for 24 ...
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DAB2IP regulates cancer stem cell phenotypes through modulating stem cell factor receptor and ZEB1.
Published: July, 2014

Abstract: Cancer stem cell (CSC), the primary source of cancer-initiating population, is involved in cancer recurrence and drug-resistant phenotypes. This study demonstrates that the loss of DAB2IP, a novel Ras-GTPase activating protein frequently found in ...
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Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.
Published: July, 2014

Abstract: Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum ...
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Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction.
Published: July, 2014

Abstract: The interior of the neuronal cell nucleus is a highly organized three-dimensional (3D) structure where regions of the genome that are linearly millions of bases apart establish sub-structures with specialized functions. To investigate neuronal chr...
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An AUG Codon Conserved for Protein Function Rather than Translational Initiation: The Story of the Protein sElk1.
Published: July, 2014

Abstract: Elk1 belongs to the ternary complex (TCF) subfamily of the ETS-domain transcription factors. Several studies have implicated an important function for Elk1 in the CNS including synaptic plasticity and cell differentiation. Whilst studying ELK1 gen...
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Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling.
Published: July, 2014

Abstract: The NuA4 histone acetyltransferase complex is required for gene regulation, cell cycle progression, and DNA repair. Dissection of the 13-subunit complex reveals that the Eaf7 subunit bridges Eaf5 with Eaf3, a H3K36me3-binding chromodomain protein,...
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Genomic organization and evolution of double minutes/homogeneously staining regions with MYC amplification in human cancer.
Published: July, 2014

Abstract: The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array...
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Heat shock factor 2 is a stress-responsive mediator of neuronal migration defects in models of fetal alcohol syndrome
Published: July, 2014

Abstract: Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal and Hsf2-...
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Heat shock factor 2 is a stress-responsive mediator of neuronal migration defects in models of fetal alcohol syndrome.
Published: July, 2014

Abstract: Fetal alcohol spectrum disorder (FASD) is a frequent cause of mental retardation. However, the molecular mechanisms underlying brain development defects induced by maternal alcohol consumption during pregnancy are unclear. We used normal and Hsf2-...
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Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways.
Published: July, 2014

Abstract: Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator ...
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Screening and identification of small molecule inhibitors of ErbB2-induced invasion
Published: July, 2014

Abstract: ERBB2 amplification and overexpression are strongly associated with invasive cancer with high recurrence and poor prognosis. Enhanced ErbB2 signaling induces cysteine cathepsin B and L expression leading to their higher proteolytic activity (zFRas...
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Comparative genome sequencing reveals chemotype-specific gene clusters in the toxigenic black mold Stachybotrys
Published: July, 2014

Abstract: Background The fungal genus Stachybotrys produces several diverse toxins that affect human health. Its strains comprise two mutually-exclusive toxin chemotypes, one producing satratoxins, which are a subclass of trichothecenes, and the other prod...
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Paradoxical role of DNA methylation in activation of FoxA2 gene expression during endoderm development.
Published: July, 2014

Abstract: The transcription factor FoxA2 is a master regulator of endoderm development and pancreatic beta cell gene expression. To elucidate the mechanisms underlying the activation of the FoxA2 gene during differentiation, we have compared the epigenetic ...
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Microsatellite Primers for the Fungi Rhizopogon kretzerae and R. salebrosus (Rhizopogonaceae) from 454 Shotgun Pyrosequencing
Published: July, 2014

Abstract: PREMISE OF THE STUDY: Rhizopogon kretzerae and R. salebrosus (Rhizopogonaceae) are ectomycorrhizal fungi symbiotic with pines and the mycoheterotrophic plant Pterospora andromedea (Ericaceae). Microsatellite loci will allow population genetic stu...
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Noncoding Transcription by Alternative RNA Polymerases Dynamically Regulates an Auxin-Driven Chromatin Loop.
Published: July, 2014

Abstract: The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidop...
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Non-Circadian Expression Masking Clock-Driven Weak Transcription Rhythms in U2OS Cells.
Published: July, 2014

Abstract: U2OS cells harbor a circadian clock but express only a few rhythmic genes in constant conditions. We identified 3040 binding sites of the circadian regulators BMAL1, CLOCK and CRY1 in the U2OS genome. Most binding sites even in promoters do not co...
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Very small deletions within the NESP55 gene in pseudohypoparathyroidism type 1b.
Published: July, 2014

Abstract: Pseudohypoparathyroidism (PHP) is caused by reduced expression of genes within the GNAS cluster, resulting in parathormone resistance. The cluster contains multiple imprinted transcripts, including the stimulatory G protein α subunit (Gs-α) and NE...
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FUS is sequestered in nuclear aggregates in ALS patient fibroblasts.
Published: July, 2014

Abstract: Mutations in the RNA-binding protein FUS have been shown to cause the neurodegenerative disease amyotrophic lateral sclerosis. We investigate whether mutant FUS protein in ALS patient-derived fibroblasts affects normal FUS functions in the nucleus...
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bPeaks: a bioinformatics tool to detect transcription factor binding sites from ChIPseq data in yeasts and other organisms with small genomes.
Published: July, 2014

Abstract: Peak calling is a critical step in ChIPseq data analysis. Choosing the correct algorithm as well as optimized parameters for a specific biological system is an essential task. In this article, we present an original peak calling method (bPeaks) sp...
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Comparison of five different RNA sources to examine the lactating bovine mammary gland transcriptome using RNA-Sequencing.
Published: July, 2014

Abstract: The objective of this study was to examine five different sources of RNA, namely mammary gland tissue (MGT), milk somatic cells (SC), laser microdissected mammary epithelial cells (LCMEC), milk fat globules (MFG) and antibody-captured milk mammary...
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Four methods of preparing mRNA 5' end libraries using the illumina sequencing platform.
Published: July, 2014

Abstract: BACKGROUND: The 5' untranslated regions of mRNA play an important role in their translation. RESULTS: Here, we describe the development of four methods of profiling mRNA 5' ends using the Illumina sequencing platform; the first method utilizes S...
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Transcriptional regulation of LUX by CBF1 mediates cold input to the circadian clock in Arabidopsis.
Published: July, 2014

Abstract: Circadian clocks allow organisms to anticipate daily changes in the environment to enhance overall fitness. Transcription factors (TFs) play a prominent role in the molecular mechanism but are incompletely described possibly due to functional redu...
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Epigenomic analysis of primary human T cells reveals enhancers associated with TH2 memory cell differentiation and asthma susceptibility.
Published: July, 2014

Abstract: A characteristic feature of asthma is the aberrant accumulation, differentiation or function of memory CD4(+) T cells that produce type 2 cytokines (TH2 cells). By mapping genome-wide histone modification profiles for subsets of T cells isolated f...
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The Histone Variant H2A.W Defines Heterochromatin and Promotes Chromatin Condensation in Arabidopsis.
Published: July, 2014

Abstract: Histone variants play crucial roles in gene expression, genome integrity, and chromosome segregation. We report that the four H2A variants in Arabidopsis define different genomic features, contributing to overall genomic organization. The histone ...
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Helicobacter pylori-induced STAT3 activation and signalling network in gastric cancer
Published: July, 2014

Abstract: Background: Helicobacter pylori (H. pylori) is the most important gastric carcinogen. However, the mechanisms of H. pylori induced gastric carcinogenesis through STAT3 activation are largely unknown. We evaluated the effects of H. pylori infection...
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Tissue specific insulator function at H19/Igf2 revealed by deletions at the imprinting control region.
Published: July, 2014

Abstract: Parent-of-origin specific expression at imprinted genes is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). This mechanism of gene regulation, where one element controls allelic expression of multiple genes, is no...
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Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways.
Published: July, 2014

Abstract: Background: In head and neck squamous cell carcinoma (HNSCC), resistance to single agent targeted therapy may be overcome by co-targeting of compensatory signaling pathways. Methods: A targeted drug screen with 120 combinations was used on 9 HNSCC...
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The interaction of MYC with the trithorax protein ASH2L promotes gene transcription by regulating H3K27 modification.
Published: July, 2014

Abstract: The appropriate expression of the roughly 30,000 human genes requires multiple layers of control. The oncoprotein MYC, a transcriptional regulator, contributes to many of the identified control mechanisms, including the regulation of chromatin, RN...
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Identification of a large protein network involved in epigenetic transmission in replicating DNA of embryonic stem cells.
Published: July, 2014

Abstract: Pluripotency of embryonic stem cells (ESCs) is maintained by transcriptional activities and chromatin modifying complexes highly organized within the chromatin. Although much effort has been focused on identifying genome-binding sites, little is k...
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The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis.
Published: July, 2014

Abstract: We provide evidence that a central player in ribosome synthesis, the ribonucleic acid helicase Prp43p, can be activated by yeast Gno1p and its human ortholog, the telomerase inhibitor PINX1. Gno1p and PINX1 expressed in yeast interact with Prp43p ...
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TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells.
Published: July, 2014

Abstract: TET1 is a 5-methylcytosine dioxygenase and its DNA demethylating activity has been implicated in pluripotency and reprogramming. However, the precise role of TET1 in DNA methylation regulation outside of developmental reprogramming is still unclea...
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The Leishmania donovani chaperone cyclophilin 40 is essential for intracellular infection independent of its stage-specific phosphorylation status.
Published: July, 2014

Abstract: During its life cycle, the protozoan pathogen Leishmania donovani is exposed to contrasting environments inside insect vector and vertebrate host, to which the parasite must adapt for extra- and intracellular survival. Combining null mutant analys...
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From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects.
Published: July, 2014

Abstract: The superordinate principles governing the transcriptome response of differentiating cells exposed to drugs are still unclear. Often, it is assumed that toxicogenomics data reflect the immediate mode of action (MoA) of drugs. Alternatively, transc...
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Feasibility of a lateral flow test for neurocysticercosis using novel up-converting nanomaterials and a lightweight strip analyzer.
Published: July, 2014

Abstract: Neurocysticercosis is a frequent parasitic infection of the human brain, occurring in most of the world, and requires imaging of the brain to diagnose. To determine the burden of disease and to simplify diagnosis, a field-friendly rapid lateral fl...
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Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes
Published: July, 2014

Abstract: Polycomb repressive complex-1 (PRC1) is essential for the epigenetic regulation of gene expression. SCML2 is a mammalian homolog of Drosophila SCM, a Polycomb-group protein that associates with PRC1. In this study, we show that SCML2A, an SCML2 is...
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Functional Conservation of the Pre-Sensor One Beta-Finger Hairpin (PS1-hp) Structures in Mini-Chromosome Maintenance Proteins of Saccharomyces cerevisiae and Archaea.
Published: July, 2014

Abstract: Mini-chromosome maintenance (MCM) proteins form complexes that are required for DNA replication and are highly conserved throughout evolution. The replicative helicase of eukaryotic organisms is composed of the six paralogs MCM2-7, which form a he...
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Genome-wide analysis of DNA 5-hmC in peripheral blood of uremia by hMeDIP-chip.
Published: July, 2014

Abstract: Abstract Background: Treatment of uremia is now dominated by dialysis; in some cases, patients are treated with dialysis for decades, but overall outcomes are disappointing. A number of studies have confirmed the relevance of several experimental ...
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Influence of ND10 Components on Epigenetic Determinants of Early KSHV Latency Establishment.
Published: July, 2014

Abstract: We have previously demonstrated that acquisition of intricate patterns of activating (H3K4me3, H3K9/K14ac) and repressive (H3K27me3) histone modifications is a hallmark of KSHV latency establishment. The precise molecular mechanisms that shape the...
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GENOME-WIDE SCREEN OF PROMOTER METHYLATION IDENTIFIES NOVEL MARKERS IN DIET-INDUCED OBESE MICE.
Published: July, 2014

Abstract: OBJECTIVE: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. METHODS: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation prof...
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DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis.
Published: July, 2014

Abstract: RNA-directed DNA methylation (RdDM) and histone H3 lysine 9 dimethylation (H3K9me2) are related transcriptional silencing mechanisms that target transposable elements (TEs) and repeats to maintain genome stability in plants. RdDM is mediated by sm...
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Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells.
Published: July, 2014

Abstract: The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune...
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3β,5α,6β-Cholestanetriol and 25-hydroxycholesterol accumulate in ATP-binding cassette transporter G1 (ABCG1)-deficiency.
Published: July, 2014

Abstract: OBJECTIVE: Oxysterols are oxidized derivatives of sterols that have cytotoxic effects and are potent regulators of diverse cellular functions. Efficient oxysterol removal by the sub-family G member 1 of the ATP-binding cassette transporters (ABCG1...
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Chromatin Profiling Reveals Regulatory Network Shifts and a Protective Role for HNF4A during Colitis.
Published: June, 2014

Abstract: Transcriptional regulatory mechanisms likely contribute to the etiology of Inflammatory Bowel Disease (IBD), as genetic variants associated with the disease are disproportionately found at regulatory elements. However, the transcription factors re...
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Pygo2 regulates β-catenin-induced activation of hair follicle stem/progenitor cells and skin hyperplasia.
Published: June, 2014

Abstract: Understanding the epigenetic mechanisms that control the activation of adult stem cells holds the promise of tissue and organ regeneration. Hair follicle stem cells have emerged as a prime model to study stem cell activation. Wnt/β-catenin signali...
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Characterization of bacteriophage communities and CRISPR profiles from dental plaque.
Published: June, 2014

Abstract: BACKGROUND: Dental plaque is home to a diverse and complex community of bacteria, but has generally been believed to be inhabited by relatively few viruses. We sampled the saliva and dental plaque from 4 healthy human subjects to determine whether...
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Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7.
Published: June, 2014

Abstract: BACKGROUND: Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which ca...
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Proteomics-Based Identification of Differentially Abundant Proteins from Human Keratinocytes Exposed to Arsenic Trioxide
Published: June, 2014

Abstract: Introduction: Arsenic i s a widely distributed environmental toxicant that can cause multi-tissue pathologies. Proteomic assays allow for the identification of biological processes modulated by arsenic in diverse tissue types. Method: The altered ...
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Otx2 and Oct4 Drive Early Enhancer Activation during Embryonic Stem Cell Transition from Naive Pluripotency.
Published: June, 2014

Abstract: Embryonic stem cells (ESCs) are unique in that they have the capacity to differentiate into all of the cell types in the body. We know a lot about the complex transcriptional control circuits that maintain the naive pluripotent state under self-re...
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MicroRNAs Establish Robustness and Adaptability of a Critical Gene Network to Regulate Progenitor Fate Decisions during Cortical Neurogenesis
Published: June, 2014

Abstract: Over the course of cortical neurogenesis, the transi- tion of progenitors from proliferation to differentia- tion requires a precise regulation of involved gene networks under varying environmental conditions. In order to identify such regulatory ...
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Listeria monocytogenes induces IFNβ expression through an IFI16-, cGAS- and STING-dependent pathway.
Published: June, 2014

Abstract: Listeria monocytogenes is a gram-positive facultative intracellular bacterium, which replicates in the cytoplasm of myeloid cells. Interferon β (IFNβ) has been reported to play an important role in the mechanisms underlying Listeria disease. Altho...
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CD1d-mediated presentation of endogenous lipid antigens by adipocytes requires microsomal triglyceride transfer protein (MTP).
Published: June, 2014

Abstract: Obesity-induced adipose tissue (AT) dysfunction results in a chronic low-grade inflammation that predisposes to the development of insulin resistance and type 2 diabetes. During the development of obesity, the AT-resident immune cell profile alter...
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Chronic inflammation induces telomere dysfunction and accelerates ageing in mice.
Published: June, 2014

Abstract: Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-κB induces premature ageing in mice. We a...
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RPLP1, a Crucial Ribosomal Protein for Embryonic Development of the Nervous System.
Published: June, 2014

Abstract: Ribosomal proteins are pivotal to development and tissue homeostasis. RP Large P1 (Rplp1) overexpression is associated with tumorigenesis. However, the physiological function of Rplp1 in mammalian development remains unknown. In this study, we dis...
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A phosphotyrosine switch determines the antitumor activity of ERβ
Published: June, 2014

Abstract: Estrogen receptors ERα and ERβ share considerable sequence homology yet exert opposite effects on breast cancer cell proliferation. While the proliferative role of ERα in breast tumors is well characterized, it is not clear whether the antitumor a...
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Immunoproteasomes Shape the Transcriptome and Regulate the Function of Dendritic Cells.
Published: June, 2014

Abstract: By regulating protein degradation, constitutive proteasomes (CPs) control practically all cellular functions. In addition to CPs, vertebrates express immunoproteasomes (IPs). The major nonredundant role ascribed to IPs is their enhanced ability to...
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Genomic mapping of cAMP receptor protein (CRPMt) in Mycobacterium tuberculosis: relation to transcriptional start sites and the role of CRPMt as a transcription factor.
Published: June, 2014

Abstract: Chromatin immunoprecipitation identified 191 binding sites of Mycobacterium tuberculosis cAMP receptor protein (CRP(Mt)) at endogenous expression levels using a specific α-CRP(Mt) antibody. Under these native conditions an equal distribution betwe...
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A role for migration-linked genes and genomic islands in divergence of a songbird.
Published: June, 2014

Abstract: Next-generation sequencing has made it possible to begin asking questions about the process of divergence at the level of the genome. For example, recently there has been a debate around the role of 'genomic islands of divergence' (i.e. blocks of ...
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Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation.
Published: June, 2014

Abstract: Chromatin compaction mediates progenitor to post-mitotic cell transitions and modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h and Snf2l are ATP-dependent chromatin remodelling proteins that assemble, reposition and...
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Epigenetic Regulation by Chromatin Activation Mark H3K4me3 in Primate Progenitor Cells within Adult Neurogenic Niche.
Published: June, 2014

Abstract: Histone 3 lysine 4 trimethylation (H3K4me3) is known to be associated with transcriptionally active or poised genes and required for postnatal neurogenesis within the subventricular zone (SVZ) in the rodent model. Previous comparisons have shown s...
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Single-base-resolution methylomes of populus trichocarpa reveal the association between DNA methylation and drought stress
Published: June, 2014

Abstract: Background: DNA methylation is an important biological form of epigenetic modification, playing key roles in plant development and environmental responses. Results: In this study, we examined single-base resolution methylomes of Populus under cont...
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ZNF143 is regulated through alternative 3'UTR isoforms.
Published: June, 2014

Abstract: ZNF143 is a ubiquitously expressed transcription factor conserved in all vertebrates, regulating genes involved in primary metabolism and cell growth. It is therefore crucial to tightly maintain the adequate level of this factor in the cell. Altho...
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Cell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral virulence regulators.
Published: June, 2014

Abstract: Zinc-finger domain transcriptional regulators regulate a myriad of functions in eukaryotes. Interestingly, ancestral versions (MucR) from Alpha-proteobacteria control bacterial virulence/symbiosis. Whether virulence regulators can also control cel...
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Breast cancer cell invasion mediated by Gα12 signaling involves expression of interleukins-6 and -8, and matrix metalloproteinase-2.
Published: June, 2014

Abstract: BACKGROUND: Recent studies on the involvement of the G12 family of heterotrimeric G proteins (Gα12 and Gα13, the products of the GNA12 and GNA13 genes, respectively) in oncogenic pathways have uncovered a link between G12 signaling and cancer prog...
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Loss of Ubp3 increases silencing, decreases unequal recombination in rDNA, and shortens the replicative life span in Saccharomyces cerevisiae.
Published: June, 2014

Abstract: Ubp3 is a conserved ubiquitin protease that acts as an antisilencing factor in MAT and telomeric regions. Here we show that ubp3∆ mutants also display increased silencing in ribosomal DNA (rDNA). Consistent with this, RNA polymerase II occupancy i...
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Two CCAAT box-binding transcription factors redundantly regulate early steps of the legume-rhizobia endosymbiosis.
Published: June, 2014

Abstract: During endosymbiotic interactions between legume plants and nitrogen-fixing rhizobia, successful root infection by bacteria and nodule organogenesis requires the perception and transduction of bacterial lipo-chitooligosaccharidic signal called Nod...
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Protein Phosphatase 2A (PP2A) Regulates Low Density Lipoprotein Uptake through Regulating Sterol Response Element-binding Protein-2 (SREBP-2) DNA Binding.
Published: June, 2014

Abstract: LDL-cholesterol (LDL-C) uptake by Ldlr is regulated at the transcriptional level by the cleavage-dependent activation of membrane-associated sterol response element-binding protein (SREBP-2). Activated SREBP-2 translocates to the nucleus, where it...
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Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment.
Published: June, 2014

Abstract: The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation ...
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Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells.
Published: June, 2014

Abstract: 5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC an...
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Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer.
Published: June, 2014

Abstract: Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the suc...
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Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease.
Published: June, 2014

Abstract: We previously demonstrated that APP epigenetically regulates Egr1 expression both in cultured neurons and in vivo. Since Egr1 is an immediate early gene involved in memory formation, we wondered whether other early genes involved in memory were re...
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A Histone Deacetylase Complex Mediates Biofilm Dispersal and Drug Resistance in Candida albicans.
Published: June, 2014

Abstract: UNLABELLED: Biofilms are resilient, surface-associated communities of cells with specialized properties (e.g., resistance to drugs and mechanical forces) that are distinct from those of suspension (planktonic) cultures. Biofilm formation by the op...
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RNAi-Mediated Gene silencing in Zebrafish Triggered by Convergent Transcription.
Published: June, 2014

Abstract: RNAi based strategies to induce gene silencing are commonly employed in numerous model organisms but have not been extensively used in zebrafish. We found that introduction of transgenes containing convergent transcription units in zebrafish embry...
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REGNET: mining context-specific human transcription networks using composite genomic information.
Published: June, 2014

Abstract: BACKGROUND: Genome-wide expression profiles reflect the transcriptional networks specific to the given cell context. However, most statistical models try to estimate the average connectivity of the networks from a collection of gene expression dat...
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Corolla Is a Novel Protein that Contributes to the Architecture of the Synaptonemal Complex of Drosophila.
Published: June, 2014

Abstract: In most organisms the synaptonemal complex (SC) connects paired homologs along their entire length during much of meiotic prophase. To better understand the structure of the SC, we aim to identify its components and to determine how each of these ...
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SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma.
Published: June, 2014

Abstract: Cancer stem cells (CSCs) have been reported in various cancers, including in skin squamous-cell carcinoma (SCC). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here we find that Sox2, a transcrip...
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COUP-TFI modifies CXCL12 and CXCR4 expression by activating EGF signaling and stimulates breast cancer cell migration.
Published: June, 2014

Abstract: BACKGROUND: The orphan receptors COUP-TF (chicken ovalbumin upstream promoter transcription factor) I and II are members of the nuclear receptor superfamily that play distinct and critical roles in vertebrate organogenesis. The involvement of COUP...
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PARG is dispensable for recovery from transient replicative stress but required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress.
Published: June, 2014

Abstract: Poly(ADP-ribosyl)ation is involved in numerous bio-logical processes including DNA repair, transcription and cell death. Cellular levels of poly(ADP-ribose) (PAR) are regulated by PAR polymerases (PARPs) and the degrading enzyme PAR glycohydrolase...
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NFAT1 and NFAT3 Cooperate with HDAC4 during Regulation of Alternative Splicing of PMCA Isoforms in PC12 Cells.
Published: June, 2014

Abstract: BACKGROUND: The bulk of human genes undergo alternative splicing (AS) upon response to physiological stimuli. AS is a great source of protein diversity and biological processes and is associated with the development of many diseases. Pheochromocyt...
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Conservation of streptococcal CRISPRs on human skin and saliva.
Published: June, 2014

Abstract: BACKGROUND: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) are utilized by bacteria to resist encounters with their viruses. Human body surfaces have numerous bacteria that harbor CRISPRs, and their content can provide clues a...
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Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation.
Published: June, 2014

Abstract: Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target si...
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Reorganization of enhancer patterns in transition from naive to primed pluripotency.
Published: June, 2014

Abstract: Naive and primed pluripotency is characterized by distinct signaling requirements, transcriptomes, and developmental properties, but both cellular states share key transcriptional regulators: Oct4, Sox2, and Nanog. Here, we demonstrate that transi...
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Retinoblastoma protein (RB) interacts with E2F3 to control terminal differentiation of Sertoli cells.
Published: June, 2014

Abstract: The retinoblastoma protein (RB) is essential for normal cell cycle control. RB function depends, at least in part, on interactions with the E2F family of DNA-binding transcription factors (E2Fs). To study the role of RB in the adult testis, a Sert...
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Hippo pathway activity influences liver cell fate.
Published: June, 2014

Abstract: The Hippo-signaling pathway is an important regulator of cellular proliferation and organ size. However, little is known about the role of this cascade in the control of cell fate. Employing a combination of lineage tracing, clonal analysis, and o...
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The HP1 Homolog Rhino Anchors a Nuclear Complex that Suppresses piRNA Precursor Splicing.
Published: June, 2014

Abstract: piRNAs guide an adaptive genome defense system that silences transposons during germline development. The Drosophila HP1 homolog Rhino is required for germline piRNA production. We show that Rhino binds specifically to the heterochromatic clusters...
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CETP inhibitors downregulate hepatic LDL receptor and PCSK9 expression in vitro and in vivo through a SREBP2 dependent mechanism.
Published: June, 2014

Abstract: BACKGROUND: CETP inhibitors block the transfer of cholesteryl ester from HDL-C to VLDL-C and LDL-C, thereby raising HDL-C and lowering LDL-C. In this study, we explored the effect of CETP inhibitors on hepatic LDL receptor (LDLR) and PCSK9 express...
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Deep sequencing reveals new aspects of progesterone receptor signaling in breast cancer cells.
Published: June, 2014

Abstract: Despite the pleiotropic effects of the progesterone receptor in breast cancer, the molecular mechanisms in play remain largely unknown. To gain a global view of the PR-orchestrated networks, we used next-generation sequencing to determine the prog...
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Frizzled 7 Expression Is Positively Regulated by SIRT1 and β-Catenin in Breast Cancer Cells.
Published: June, 2014

Abstract: The Wnt signaling pathway is often chronically activated in diverse human tumors, and the Frizzled (FZD) family of receptors for Wnt ligands, are central to propagating oncogenic signals in a β-catenin-dependent and independent manner. SIRT1 is a ...
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Insulin regulates carboxypeptidase E by modulating translation initiation scaffolding protein eIF4G1 in pancreatic β cells.
Published: June, 2014

Abstract: Insulin resistance, hyperinsulinemia, and hyperproinsulinemia occur early in the pathogenesis of type 2 diabetes (T2D). Elevated levels of proinsulin and proinsulin intermediates are markers of β-cell dysfunction and are strongly associated with d...
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Functional Analysis of the TRIB1 Associated Locus Linked to Plasma Triglycerides and Coronary Artery Disease.
Published: June, 2014

Abstract: BACKGROUND: The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid-associated single nucleotide polymorphisms (SNPs), identified by genome-wide associ...
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Chronic alcohol consumption leads to neurochemical changes in the nucleus accumbens that are not fully reversed by withdrawal.
Published: June, 2014

Abstract: Neuropeptide Y (NPY)- and acetylcholine-containing interneurons of the nucleus accumbens (NAc) seem to play a major role in the rewarding effects of alcohol. This study investigated the relationship between chronic alcohol consumption and subseque...
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Differential regulation of Gli proteins by Sufu in the lung affects PDGF signaling and myofibroblast development.
Published: June, 2014

Abstract: Mammalian Hedgehog (Hh) signaling relies on three Gli transcription factors to mediate Hh responses. This process is controlled in part by a major negative regulator, Sufu, through its effects on Gli protein level, distribution and activity. In th...
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A specific polymorphism in Mycobacterium tuberculosis H37Rv causes differential ESAT-6 expression and identifies WhiB6 as a novel ESX-1 component.
Published: June, 2014

Abstract: The ESX-1 secreted virulence factor ESAT-6 is one of the major and most well-studied virulence factors of Mycobacterium tuberculosis given that its inactivation severely attenuates virulent mycobacteria. In this work we show that clinical isolates...
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Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
Published: June, 2014

Abstract: In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying e...
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The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome.
Published: June, 2014

Abstract: Parental imprinting is a form of epigenetic regulation that results in parent-of-origin differential gene expression. To study Prader-Willi syndrome (PWS), a developmental imprinting disorder, we generated case-derived induced pluripotent stem cel...
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MOZ-Mediated Repression of p16(INK) (4) (a) Is Critical for the Self-Renewal of Neural and Hematopoietic Stem Cells.
Published: June, 2014

Abstract: Although inhibition of p16(INK4a) expression is critical to preserve the proliferative capacity of stem cells, the molecular mechanisms responsible for silencing p16(INK4a) expression remain poorly characterized. Here, we show that the histone ace...
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BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export factor PCID2.
Published: June, 2014

Abstract: Genome instability is central to ageing, cancer and other diseases. It is not only proteins involved in DNA replication or the DNA damage response (DDR) that are important for maintaining genome integrity: from yeast to higher eukaryotes, mutation...
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Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system.
Published: June, 2014

Abstract: Genome manipulation in the malaria parasite Plasmodium falciparum remains largely intractable and improved genomic tools are needed to further understand pathogenesis and drug resistance. We demonstrated the CRISPR-Cas9 system for use in P. falcip...
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CPF-Associated Phosphatase Activity Opposes Condensin-Mediated Chromosome Condensation.
Published: June, 2014

Abstract: Functional links connecting gene transcription and condensin-mediated chromosome condensation have been established in species ranging from prokaryotes to vertebrates. However, the exact nature of these links remains misunderstood. Here we show in...
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New lung cancer panel for high-throughput targeted resequencing.
Published: June, 2014

Abstract: We present a new next-generation sequencing-based method to identify somatic mutations of lung cancer. It is a comprehensive mutation profiling protocol to detect somatic mutations in 30 genes found frequently in lung adenocarcinoma. The total len...
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Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells.
Published: June, 2014

Abstract: BACKGROUND & AIMS: Thousands of long intergenic non-protein coding RNAs (lincRNAs) have been identified in mammals via genome-wide sequencing studies. Many are functional, but are expressed aberrantly by cancer cells. We investigated whether level...
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Phylogenomics of the plant family Araceae.
Published: June, 2014

Abstract: The biogeography, chromosome number evolution, pollination biology and evolutionary history of the plant family Araceae have recently become much clearer (Cabrera et al., 2008; Chartier et al., 2013; Cusimano et al., 2011, 2012; Nauheimer et al., ...
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Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression.
Published: June, 2014

Abstract: The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but the corresponding regulatory mechanisms are incompletely understood. To study the re...
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Engineered zinc-finger transcription factors activate OCT4 (POU5F1), SOX2, KLF4, c-MYC (MYC) and miR302/367.
Published: June, 2014

Abstract: Artificial transcription factors are powerful tools for regulating gene expression. Here we report results with engineered zinc-finger transcription factors (ZF-TFs) targeting four protein-coding genes, OCT4, SOX2, KLF4 and c-MYC, and one noncodin...
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Hydroxymethylation and DNA methylation profiles in the prefrontal cortex of the non-human primate rhesus macaque and the impact of maternal deprivation on hydroxymethylation.
Published: May, 2014

Abstract: 5-Hydroxymethylcytosine (5hmC) is abundant in the brain, suggesting an important role in epigenetic control of neuronal functions. In this paper, we show that 5hmC and 5-methylcytosine (5mC) levels are coordinately distributed in gene promoters of...
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Membrane-Bound Methyltransferase Complex VapA-VipC-VapB Guides Epigenetic Control of Fungal Development.
Published: May, 2014

Abstract: Epigenetic and transcriptional control of gene expression must be coordinated in response to external signals to promote alternative multicellular developmental programs. The membrane-associated trimeric complex VapA-VipC-VapB controls a signal tr...
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Fat specific protein 27 inhibits lipolysis by facilitating the inhibitory effect of Egr1 on transcription of adipose triglyceride lipase.
Published: May, 2014

Abstract: Lipolysis in fat tissue represents a major source of circulating fatty acids. Previously, we have found that lipolysis in adipocytes is controlled by early growth response transcription factor Egr1 that directly inhibits transcription of adipose t...
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A genome-wide analysis of Cas9 binding specificity using ChIP-seq and targeted sequence capture
Published: May, 2014

Abstract: Clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided nucleases have gathered considerable excitement as a tool for genome engineering. However, questions remain about the specificity of their target site recognition. Most p...
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Quiescence-Induced LncRNAs Trigger H4K20 Trimethylation and Transcriptional Silencing.
Published: May, 2014

Abstract: A complex network of regulatory pathways links transcription to cell growth and proliferation. Here we show that cellular quiescence alters chromatin structure by promoting trimethylation of histone H4 at lysine 20 (H4K20me3). In contrast to peric...
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Regulating Set-β's Subcellular Localization Toggles Its Function between Inhibiting and Promoting Axon Growth and Regeneration.
Published: May, 2014

Abstract: The failure of the CNS neurons to regenerate axons after injury or stroke is a major clinical problem. Transcriptional regulators like Set-β are well positioned to regulate intrinsic axon regeneration capacity, which declines developmentally in ma...
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Altered oral viral ecology in association with periodontal disease.
Published: May, 2014

Abstract: UNLABELLED: The human oral cavity is home to a large and diverse community of viruses that have yet to be characterized in patients with periodontal disease. We recruited and sampled saliva and oral biofilm from a cohort of humans either periodont...
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Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer
Published: May, 2014

Abstract: Tumour cells sustain their high proliferation rate through metabolic reprogramming, whereby cellular metabolism shifts from oxidative phosphorylation to aerobic glycolysis, even under normal oxygen levels. Hypoxia-inducible factor 1A (HIF1A) is a ...
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Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis uncovers broad changes in chromatin structure resulting from hexavalent chromium exposure.
Published: May, 2014

Abstract: The ability of chromatin to switch back and forth from open euchromatin to closed heterochromatin is vital for transcriptional regulation and genomic stability, but its dynamic structure is subject to disruption by exposure to environmental agents...
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Expanding the chemical diversity of natural esters by engineering a polyketide-derived pathway into Escherichia coli.
Published: May, 2014

Abstract: Microbial fatty acid (FA)-derived molecules have emerged as promising alternatives to petroleum-based chemicals for reducing dependence on fossil hydrocarbons. However, native FA biosynthetic pathways often yield limited structural diversity, and ...
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Discovery of transgene insertion sites by high throughput sequencing of mate pair libraries.
Published: May, 2014

Abstract: BACKGROUND: Transgenesis by random integration of a transgene into the genome of a zygote has become a reliable and powerful method for the creation of new mouse strains that express exogenous genes, including human disease genes, tissue specific ...
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Homeostatic maintenance of allele-specific p16 methylation in cancer cells accompanied by dynamic focal methylation and hydroxymethylation.
Published: May, 2014

Abstract: AIM: p16 Methylation frequently occurs in carcinogenesis. While it has been hypothesized that the p16 methylation states are dynamically maintained in cancer cells, direct evidence supporting this hypothesis has not been available until now. METHO...
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Parallel profiling of the transcriptome, cistrome, and epigenome in the cellular response to ionizing radiation.
Published: May, 2014

Abstract: The DNA damage response (DDR) is a vast signaling network that is robustly activated by DNA double-strand breaks, the critical lesion induced by ionizing radiation (IR). Although much of this response operates at the protein level, a critical comp...
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Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency.
Published: May, 2014

Abstract: Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. Here we map acquired genomic alterations in human and mouse ...
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Androgen-dependent Sertoli cell tight junction remodeling is mediated by multiple tight junction components.
Published: May, 2014

Abstract: Sertoli cell tight junctions (SCTJs) of the seminiferous epithelium create a specialized microenvironment in the testis to aid differentiation of spermatocytes and spermatids from spermatogonial stem cells. SCTJs must be chronically broken and re-...
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IL-22 negatively regulates Helicobacter pylori-induced CCL20 expression in gastric epithelial cells.
Published: May, 2014

Abstract: Helicobacter pylori is a Gram-negative bacterium that infects the human gastric mucosa and causes various gastric diseases. H. pylori infection induces the production of inflammatory chemokine CCL20 in gastric mucosa and leads to gastric inflammat...
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Transmission from centenarians to their offspring of mtDNA heteroplasmy revealed by ultra-deep sequencing
Published: May, 2014

Abstract: The role that mtDNA heteroplasmy plays in healthy aging, familial longevity and the heritability patterns of low levels heteroplasmy in the elderly are largely unknown. We analyzed the low levels of mtDNA heteroplasmy in blood in a cohort of cente...
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IL-15 regulates Bcl-2 family members Bim and Mcl-1 through JAK/STAT and PI3K/AKT pathways in T cells.
Published: May, 2014

Abstract: Maintenance of T cells is determined by their survival capacity, which is regulated by Bcl-2 proteins. Cytokines signalling through the common gamma chains such as IL-2, IL-7 and IL-15 are important for T-cell survival but how these cytokines dete...
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Genomic analysis of the emergence of 20th century epidemic dysentery.
Published: May, 2014

Abstract: BACKGROUND: Shigella dysenteriae type 1 (Sd1) causes recurrent epidemics of dysentery associated with high mortality in many regions of the world. Sd1 infects humans at very low infectious doses (10 CFU), and treatment is complicated by the rapid ...
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The Transcriptional Regulators TAZ and YAP Direct Transforming Growth Factor β-induced Tumorigenic Phenotypes in Breast Cancer Cells.
Published: May, 2014

Abstract: Uncontrolled transforming growth factor-β (TGFβ) signaling promotes aggressive metastatic properties in late-stage breast cancers. However, how TGFβ-mediated cues are directed to induce tumorigenic events is poorly understood, particularly given t...
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Insights into how Spt5 functions in transcription elongation and repressing transcription coupled DNA repair.
Published: May, 2014

Abstract: Spt5, a transcription elongation factor, and Rpb4, a subunit of RNA polymerase II (RNAP II) that forms a subcomplex with Rpb7, play important roles in transcription elongation and repression of transcription coupled DNA repair (TCR) in eukaryotic ...
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Identification of regulators of the three-dimensional polycomb organization by a microscopy-based genome-wide RNAi screen.
Published: May, 2014

Abstract: Polycomb group (PcG) proteins dynamically define cellular identities through epigenetic repression of key developmental genes. PcG target gene repression can be stabilized through the interaction in the nucleus at PcG foci. Here, we report the res...
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Dendritic cell development requires histone deacetylase activity.
Published: May, 2014

Abstract: DCs develop from multipotent progenitors (MPPs), which commit into DC-restricted common dendritic cell progenitors (CDPs). CDPs further differentiate into classical DCs (cDCs) and plasmacytoid DCs (pDCs). Here, we studied the impact of histone ace...
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The extent of error-prone replication-restart by homologous recombination is controlled by Exo1 and checkpoint proteins
Published: May, 2014

Abstract: Genetic instability, a hallmark of cancer, can occur when the replication machinery encounters a barrier. The intra-S phase checkpoint maintains stalled replication forks in a replication-competent configuration by phosphorylating replisome compon...
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Biogeography and phylogenomics of New World Bambusoideae (Poaceae), revisited.
Published: May, 2014

Abstract: • Premise of the study: New World Bambusoideae have only recently been studied in a phylogenomic context. Plastome sequences were determined and analyzed from Arundinaria appalachiana, A. tecta, and Olyra latifolia, to refine our knowledge of thei...
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Myostatin Regulates Energy Homeostasis in the Heart and Prevents Heart Failure.
Published: May, 2014

Abstract: RATIONALE: Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes including enhanced insulin sensitivity. However, the function of Myostatin in the heart is barely understood although it is upregul...
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Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells.
Published: May, 2014

Abstract: Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is ...
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Enriched domain detector: a program for detection of wide genomic enrichment domains robust against local variations.
Published: May, 2014

Abstract: Nuclear lamins contact the genome at the nuclear periphery through large domains and are involved in chromatin organization. Among broad peak calling algorithms available to date, none are suited for mapping lamin-genome interactions genome wide. ...
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EXPRSS: an Illumina based high-throughput expression-profiling method to reveal transcriptional dynamics.
Published: May, 2014

Abstract: BACKGROUND: Next Generation Sequencing technologies have facilitated differential gene expression analysis through RNA-seq and Tag-seq methods. RNA-seq has biases associated with transcript lengths, lacks uniform coverage of regions in mRNA and re...
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Thyroid hormone induction of human cholesterol 7 alpha-hydroxylase (Cyp7a1) in vitro.
Published: May, 2014

Abstract: Thyroid hormone (TH) modulates serum cholesterol by acting on TH receptor β1 (TRβ1) in liver to regulate metabolic gene sets. In rodents, one important TH regulated step involves induction of Cyp7a1, an enzyme in the cytochrome P450 family, which ...
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Highly efficient differentiation of embryonic stem cells into adipocytes by ascorbic acid.
Published: May, 2014

Abstract: Adipocyte differentiation and function have become the major research targets due to the increasing interest in obesity and related metabolic conditions. Although, late stages of adipogenesis have been extensively studied, the early phases remain ...
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MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells.
Published: May, 2014

Abstract: Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence line...
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Reassessment of QTLs for Late Blight Resistance in the Tomato Accession L3708 Using a Restriction Site Associated DNA (RAD) Linkage Map and Highly Aggressive Isolates of Phytophthora infestans
Published: May, 2014

Abstract: omato late blight caused by the oomycete pathogen Phytophthora infestans (Mont.) de Bary is a major threat to tomato production in cool and wet environments. Intensified outbreaks of late blight have been observed globally from the 1980s, and are ...
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The plant metacaspase AtMC1 in pathogen-triggered programmed cell death and aging: functional linkage with autophagy.
Published: May, 2014

Abstract: Autophagy is a major nutrient recycling mechanism in plants. However, its functional connection with programmed cell death (PCD) is a topic of active debate and remains not well understood. Our previous studies established the plant metacaspase At...
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Trrap-dependent histone acetylation specifically regulates cell-cycle gene transcription to control neural progenitor fate decisions.
Published: May, 2014

Abstract: Fate decisions in neural progenitor cells are orchestrated via multiple pathways, and the role of histone acetylation in these decisions has been ascribed to a general function promoting gene activation. Here, we show that the histone acetyltransf...
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DNA hypermethylation in prostate cancer is a consequence of aberrant epithelial differentiation and hyperproliferation.
Published: May, 2014

Abstract: Prostate cancer (CaP) is mostly composed of luminal-like differentiated cells, but contains a small subpopulation of basal cells (including stem-like cells), which can proliferate and differentiate into luminal-like cells. In cancers, CpG island h...
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The Ah Receptor Recruits IKKα to Its Target Binding Motifs to Phosphorylate Serine-10 in Histone H3 Required for Transcriptional Activation.
Published: May, 2014

Abstract: Aryl hydrocarbon receptor (AHR) activation by xenobiotic ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is key to their toxicity. Following activation and nuclear translocation, AHR heterodimerizes with the AHR nuclear translocator (AR...
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Early-life stress reduces DNA methylation of the pomc gene in male mice.
Published: May, 2014

Abstract: Early-life stress (ELS) increases the vulnerability thresholds for stress-related diseases such as major depression and anxiety by inducing alterations in the structure and function of neural circuits and endocrine pathways. We previously demonstr...
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The myc 3' wnt-responsive element suppresses colonic tumorigenesis.
Published: May, 2014

Abstract: Mutations in components of the Wnt/β-catenin signaling pathway are commonly found in colorectal cancers, and these mutations cause aberrant expression of genes controlled by Wnt-responsive DNA elements (WREs). While the c-Myc proto-oncogene (Myc) ...
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Function-based identification of mammalian enhancers using site-specific integration.
Published: May, 2014

Abstract: The accurate and comprehensive identification of functional regulatory sequences in mammalian genomes remains a major challenge. Here we describe site-specific integration fluorescence-activated cell sorting followed by sequencing (SIF-seq), an un...
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Unraveling vitamin B12-responsive gene regulation in algae.
Published: May, 2014

Abstract: Photosynthetic microalgae play a vital role in primary productivity and biogeochemical cycling in both marine and freshwater systems across the globe. However, the growth of these cosmopolitan organisms depends on the bioavailability of nutrients ...
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CD4(+) T cell lineage integrity is controlled by the histone deacetylases HDAC1 and HDAC2.
Published: May, 2014

Abstract: Molecular mechanisms that maintain lineage integrity of helper T cells are largely unknown. Here we show histone deacetylases 1 and 2 (HDAC1 and HDAC2) as crucial regulators of this process. Loss of HDAC1 and HDAC2 during late T cell development l...
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Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin.
Published: May, 2014

Abstract: Obesity and resistance to insulin are closely associated with the development of low-grade inflammation. Interleukin 6 (IL-6) is linked to obesity-associated inflammation; however, its role in this context remains controversial. Here we found that...
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Double-Wall Carbon Nanotubes for Wide-Band, Ultrafast Pulse Generation.
Published: May, 2014

Abstract: We demonstrate wide-band ultrafast optical pulse generation at 1, 1.5, and 2 μm using a single-polymer composite saturable absorber based on double-wall carbon nanotubes (DWNTs). The freestanding optical quality polymer composite is prepared from ...
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Monitoring in vivo reversible cysteine oxidation in proteins using ICAT and mass spectrometry.
Published: May, 2014

Abstract: Reversible thiol oxidation of cysteine residues occurs in many intracellular catalytic and signaling processes. Here we describe an optimized protocol, which can be completed in ∼5 d, to unambiguously identify specific cysteine residues that are t...
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Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis.
Published: May, 2014

Abstract: Treatment and control of schistosomiasis relies on the only available drug, praziquantel, and the search for alternative chemotherapeutic agents is therefore urgent. Egg production is required for the transmission and immunopathology of schistosom...
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R-loops associated with triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome.
Published: May, 2014

Abstract: Friedreich ataxia (FRDA) and Fragile X syndrome (FXS) are among 40 diseases associated with expansion of repeated sequences (TREDs). Although their molecular pathology is not well understood, formation of repressive chromatin and unusual DNA struc...
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Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia.
Published: April, 2014

Abstract: BACKGROUND: Aberrant DNA methylation is frequently found in human malignancies including acute myeloid leukemia (AML). While most studies focus on later disease stages, the onset of aberrant DNA methylation events and their dynamics during leukemi...
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Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis.
Published: April, 2014

Abstract: The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is critical for establishing lineage-specific chromatin states during early mammalian development. However, the role of SMARCA4 in tissue-specific gene regulation during embryo...
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Primary vitamin D receptor target genes as biomarkers for the vitamin D3 status in the hematopoietic system.
Published: April, 2014

Abstract: Vitamin D3 belongs to the few nutritional compounds that has, via the binding of its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) to the transcription factor vitamin D receptor (VDR), a direct effect on gene regulation. The relation of thous...
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Breast tumor specific mutation in GATA3 affects physiological mechanisms regulating transcription factor turnover.
Published: April, 2014

Abstract: BACKGROUND: The transcription factor GATA3 is a favorable prognostic indicator in estrogen receptor-alpha (ERalpha)-positive breast tumors in which it participates with ERalpha and FOXA1 in a complex transcriptional regulatory program driving tumo...
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Dynamic ER Interactomes Control the Estrogen-Responsive Trefoil Factor (TFF) Locus Cell-Specific Activities.
Published: April, 2014

Abstract: Estradiol signaling is ideally suited for analyzing molecular and functional linkages between the different layers of information directing transcriptional regulations: DNA sequence, chromatin modifications and the spatial organization of the geno...
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The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.
Published: April, 2014

Abstract: In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-...
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Targeting vertebrate intron-encoded box C/D 2'-O-methylation guide RNAs into the Cajal body.
Published: April, 2014

Abstract: Post-transcriptional pseudouridylation and 2'-O-methylation of splicesomal small nuclear ribonucleic acids (snRNAs) is mediated by box H/ACA and box C/D small Cajal body (CB)-specific ribonucleoproteins (scaRNPs), respectively. The WD-repeat prote...
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Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells.
Published: April, 2014

Abstract: Bacterial type II CRISPR-Cas9 systems have been widely adapted for RNA-guided genome editing and transcription regulation in eukaryotic cells, yet their in vivo target specificity is poorly understood. Here we mapped genome-wide binding sites of a...
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Specificity Protein 1 (Sp1) Maintains Basal Epithelial Expression of the miR-200 Family: IMPLICATIONS FOR EPITHELIAL-MESENCHYMAL TRANSITION.
Published: April, 2014

Abstract: Epithelial-mesenchymal transition (EMT) is required for the specification of tissues during embryonic development and is recapitulated during the metastatic progression of tumors. The miR-200 family plays a critical role in enforcing the epithelia...
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Gene-Specific Methylation Control of H3K9 and H3K36 on Neurotrophic BDNF versus Astroglial GFAP Genes by KDM4A/C Regulates Neural Stem Cell Differentiation.
Published: April, 2014

Abstract: Neural stem cell (NSC) state and fate depend on spatially and temporally synchronized transcriptional and epigenetic regulation of the expression of extrinsic signaling factors and intrinsic cell-specific genes, but the functional roles for chroma...
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Genome-Wide and Gene-Specific Epigenomic Platforms for Hepatocellular Carcinoma Biomarker Development Trials
Published: April, 2014

Abstract: The majority of the epigenomic reports in hepatocellular carcinoma have focused on identifying novel differentially methylated drivers or passengers of the oncogenic process. Few reports have considered the technologies in place for clinical trans...
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The CpG Island Encompassing the Promoter and First Exon of Human DNMT3L Gene Is a PcG/TrX Response Element (PRE).
Published: April, 2014

Abstract: DNMT3L, a member of DNA methyltransferases family, is present only in mammals. As it provides specificity to the action of de novo methyltransferases, DNMT3A and DNMT3B and interacts with histone H3, DNMT3L has been invoked as the molecule that ca...
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CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice.
Published: April, 2014

Abstract: Haploinsufficiency for CHD7, an ATP-dependent nucleosome remodeling factor, is the leading cause of CHARGE syndrome. While congenital heart defects (CHDs) are major clinical features of CHARGE syndrome, affecting >75% of patients, it remains uncle...
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Suv39h1 mediates AP-2α-dependent inhibition of C/EBPα expression during adipogenesis.
Published: April, 2014

Abstract: Previous studies show that CCAAT/enhancer-binding protein α (C/EBPα) plays a very important role during adipocyte terminal differentiation and that AP-2α (Activator Protein 2α) acts as a repressor to delay the expression of C/EBPα. However, the me...
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Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1.
Published: April, 2014

Abstract: Genetic deficiencies in transcription factors can lead to the loss of certain types of cells and tissue. The steroidogenic tissue-specific nuclear receptor Ad4BP/SF-1 (NR5A1) is one such gene, because mice in which this gene is disrupted fail to d...
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Acupuncture Promotes Angiogenesis after Myocardial Ischemia through H3K9 Acetylation Regulation at VEGF Gene.
Published: April, 2014

Abstract: BACKGROUND: Acupuncture exerts cardioprotective effects on several types of cardiac injuries, especially myocardial ischemia (MI), but the mechanisms have not yet been well elucidated. Angiogenesis mediated by VEGF gene expression and its modifica...
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Histone Deacetylase 1 and p300 Can Directly Associate with Chromatin and Compete for Binding in a Mutually Exclusive Manner.
Published: April, 2014

Abstract: Lysine acetyltransferases (KATs) and histone deacetylases (HDACs) are important epigenetic modifiers and dynamically cycled on active gene promoters to regulate transcription. Although HDACs are recruited to gene promoters and DNA hypersensitive s...
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Rif1 controls DNA replication timing in yeast through the PP1 phosphatase Glc7.
Published: April, 2014

Abstract: The Rif1 protein, originally identified as a telomere-binding factor in yeast, has recently been implicated in DNA replication control from yeast to metazoans. Here, we show that budding yeast Rif1 protein inhibits activation of prereplication com...
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Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency.
Published: April, 2014

Abstract: Accumulating evidences demonstrated that early postnatal maternal separation induced remarkable social and memory defects in the adult rodents. Early-life stress induced long-lasting functional adaptation of neuroendocrine hypothalamic-pituitary-a...
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ZBED6 Modulates the Transcription of Myogenic Genes in Mouse Myoblast Cells.
Published: April, 2014

Abstract: ZBED6 is a recently discovered transcription factor, unique to placental mammals, that has evolved from a domesticated DNA transposon. It acts as a repressor at the IGF2 locus. Here we show that ZBED6 acts as a transcriptional modulator in mouse m...
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Characterization of an archaeal two-component system that regulates methanogenesis in Methanosaeta harundinacea.
Published: April, 2014

Abstract: Two-component signal transduction systems (TCSs) are a major mechanism used by bacteria in response to environmental changes. Although many sequenced archaeal genomes encode TCSs, they remain poorly understood. Previously, we reported that a metha...
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The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression.
Published: April, 2014

Abstract: The transcription factor E4bp4 (Nfil3) is essential for natural killer (NK) cell production. Here, we show that E4bp4 is required at the NK lineage commitment point when NK progenitors develop from common lymphoid progenitors (CLPs) and that E4bp4...
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Multisite phosphorylation of the Sum1 transcriptional repressor by S-phase kinases controls exit from meiotic prophase in yeast.
Published: April, 2014

Abstract: Activation of the meiotic transcription factor Ndt80 is a key regulatory transition in the life-cycle of Saccharomyces cerevisiae because it triggers exit from pachytene and entry into meiosis. The NDT80 promoter is held inactive by a complex cont...
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Whole Exome Sequencing Identifies Recessive PKHD1 Mutations in a Chinese Twin Family with Caroli Disease.
Published: April, 2014

Abstract: BACKGROUND: Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlati...
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Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period.
Published: April, 2014

Abstract: The complex relationship between ontogeny and phylogeny has been the subject of attention and controversy since von Baer's formulations in the 19th century. The classic concept that embryogenesis progresses from clade general features to species s...
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YY1 Acts as a Transcriptional Activator of Hoxa5 Gene Expression in Mouse Organogenesis.
Published: April, 2014

Abstract: The Hox gene family encodes homeodomain-containing transcriptional regulators that confer positional information to axial and paraxial tissues in the developing embryo. The dynamic Hox gene expression pattern requires mechanisms that differentiall...
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Protein quantitative trait Loci identify novel candidates modulating cellular response to chemotherapy.
Published: April, 2014

Abstract: Annotating and interpreting the results of genome-wide association studies (GWAS) remains challenging. Assigning function to genetic variants as expression quantitative trait loci is an expanding and useful approach, but focuses exclusively on mRN...
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USP7 attenuates hepatic gluconeogenesis through modulation of FoxO1 gene promoter occupancy.
Published: April, 2014

Abstract: Hepatic forkhead protein FoxO1 is a key component of systemic glucose homeostasis via its ability to regulate the transcription of rate-limiting enzymes in gluconeogenesis. Important in the regulation of FoxO1 transcriptional activity are the modi...
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Intronic DNA elements regulate Nrf-2 chemical responsiveness of the human microsomal epoxide hydrolase gene (EPHX1) through a far upstream alternative promoter.
Published: April, 2014

Abstract: In humans, microsomal epoxide hydrolase (mEH) contributes important biological functions that underlie both detoxification and bioactivation fates arising from exposures to foreign chemicals. Previously, we discovered that human mEH gene transcrip...
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ApoER2 processing by presenilin-1 modulates reelin expression.
Published: April, 2014

Abstract: The reelin signaling protein and its downstream components have been associated with synaptic plasticity and neurotransmission. The reelin signaling pathway begins with the binding of reelin to the transmembrane lipoprotein receptor apolipoprotein...
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LORD-Q: a long-run real-time PCR-based DNA-damage quantification method for nuclear and mitochondrial genome analysis.
Published: April, 2014

Abstract: DNA damage is tightly associated with various biological and pathological processes, such as aging and tumorigenesis. Although detection of DNA damage is attracting increasing attention, only a limited number of methods are available to quantify D...
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Length-dependent processing of telomeres in the absence of telomerase.
Published: April, 2014

Abstract: In the absence of telomerase, telomeres progressively shorten with every round of DNA replication, leading to replicative senescence. In telomerase-deficient Saccharomyces cerevisiae, the shortest telomere triggers the onset of senescence by activ...
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CpG domains downstream of TSSs promote high levels of gene expression.
Published: April, 2014

Abstract: CpG dinucleotides are known to play a crucial role in regulatory domains, affecting gene expression in their natural context. Here, we demonstrate that intragenic CpG frequency and distribution impacts transgene and genomic gene expression levels ...
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The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by L-histidine.
Published: April, 2014

Abstract: Carnosine (β-alanyl-L-histidine) is a naturally occurring dipeptide that shows antineoplastic effects in cell culture as well as in animal experiments. Since its mode of action and the targets at the molecular level have not yet been elucidated, w...
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Suppression of intragenic transcription requires the MOT1 and NC2 regulators of TATA-binding protein.
Published: April, 2014

Abstract: Chromatin structure in transcribed regions poses a barrier for intragenic transcription. In a comprehensive study of the yeast chromatin remodelers and the Mot1p-NC2 regulators of TATA-binding protein (TBP), we detected synthetic genetic interacti...
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Folic acid stimulation of neural stem cell proliferation is associated with altered methylation profile of PI3K/Akt/CREB.
Published: April, 2014

Abstract: Proliferation of neural stem cells (NSCs) is required for development and repair in the nervous system. NSC amplification in vitro is a necessary step towards using NSC transplantation therapy to treat neurodegenerative diseases. Folic acid (FA) h...
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Mapping of six somatic linker histone H1 variants in human breast cancer cells uncovers specific features of H1.2.
Published: April, 2014

Abstract: Seven linker histone H1 variants are present in human somatic cells with distinct prevalence across cell types. Despite being key structural components of chromatin, it is not known whether the different variants have specific roles in the regulat...
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Transcriptional Derepression of the ERVWE1 Locus following Influenza A Virus Infection.
Published: April, 2014

Abstract: UNLABELLED: Syncytin-1, a fusogenic protein encoded by a human endogenous retrovirus of the W family (HERV-W) element (ERVWE1), is expressed in the syncytiotrophoblast layer of the placenta. This locus is transcriptionally repressed in adult tissu...
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HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters.
Published: April, 2014

Abstract: Active positive transcription elongation factor b (P-TEFb) is essential for cellular and human immunodeficiency virus type 1 (HIV-1) transcription elongation. CTIP2 represses P-TEFb activity in a complex containing 7SK RNA and HEXIM1. Recently, th...
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Anp32e, a higher eukaryotic histone chaperone directs preferential recognition for H2A.Z.
Published: April, 2014

Abstract: H2A.Z is a highly conserved histone variant in all species. The chromatin deposition of H2A.Z is specifically catalyzed by the yeast chromatin remodeling complex SWR1 and its mammalian counterpart SRCAP. However, the mechanism by which H2A.Z is pr...
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High-throughput sequencing exclusively identified a novel Torque teno virus genotype in serum of a patient with fatal fever.
Published: April, 2014

Abstract: Torque teno virus (TTV) has been found to be prevalent world-wide in healthy populations and in patients with various diseases, but its etiological role has not yet been determined. Using high-throughput unbiased sequencing to screen for viruses i...
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MBD4 cooperates with DNMT1 to mediate methyl-DNA repression and protects mammalian cells from oxidative stress.
Published: April, 2014

Abstract: Oxidative stress induces genome-wide remodeling of the chromatin structure. In this study, we identify Methyl-CpG Binding Protein 4 (MBD4), a multifunctional enzyme involved in DNA demethylation, base excision repair, and gene expression regulatio...
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Rad51-Rad52 mediated maintenance of centromeric chromatin in Candida albicans.
Published: April, 2014

Abstract: Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence. However, the non-genetic determinants of centromere identity are not clearly defined. While multiple mechanisms, individually or in concert, m...
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TAp73 is essential for germ cell adhesion and maturation in testis.
Published: March, 2014

Abstract: A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the...
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High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma.
Published: March, 2014

Abstract: Sex determining region Y-box 11 (SOX11) expression is specific for mantle cell lymphoma (MCL) as compared with other non-Hodgkin's lymphomas. However, the function and direct-binding targets of SOX11 in MCL are largely unknown. We used high-resolu...
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Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline.
Published: March, 2014

Abstract: Mapping genome-wide data to human subtelomeres has been problematic due to the incomplete assembly and challenges of low-copy repetitive DNA elements. Here, we provide updated human subtelomere sequence assemblies that were extended by filling tel...
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Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.
Published: March, 2014

Abstract: Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n...
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Disturbed subsurface microbial communities follow equivalent trajectories despite different structural starting points.
Published: March, 2014

Abstract: Microbial community structure, and niche and neutral processes can all influence response to disturbance. Here, we provide experimental evidence for niche versus neutral and founding community effects during a bioremediation-related organic carbon...
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Modelling mutational landscapes of human cancers in vitro.
Published: March, 2014

Abstract: Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine...
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High-throughput quantitative proteomic analysis of dengue virus type 2 infected A549 cells.
Published: March, 2014

Abstract: Disease caused by dengue virus is a global health concern with up to 390 million individuals infected annually worldwide. There are no vaccines or antiviral compounds available to either prevent or treat dengue disease which may be fatal. To incre...
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Hic-5 influences genomic and non-genomic actions of the androgen receptor in prostate myofibroblasts.
Published: March, 2014

Abstract: There is extensive knowledge of androgen receptor (AR) signaling in cancer cells, but less regarding androgen action in stromal cells of the tumor microenvironment. We report here the genome-wide effects of a stromal cell specific molecular adapte...
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GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice.
Published: March, 2014

Abstract: Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT) is a rare genetic disorder caused by mutations ...
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Calcineurin/NFAT signaling represses genes Vamp1 and Vamp2 via PMCA-dependent mechanism during dopamine secretion by Pheochromocytoma cells.
Published: March, 2014

Abstract: BACKGROUND: Plasma membrane Ca(2+)-ATPases (PMCA) extrude Ca(2+) ions out of the cell and contribute to generation of calcium oscillations. Calcium signaling is crucial for transcriptional regulation of dopamine secretion by neuroendocrine PC12 ce...
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Identification of protein partners in mycobacteria using a single-step affinity purification method.
Published: March, 2014

Abstract: Tuberculosis is a leading cause of death in developing countries. Efforts are being made to both prevent its spread and improve curability rates. Understanding the biology of the bacteria causing the disease, Mycobacterium tuberculosis (M. tubercu...
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Hmga2 is required for canonical WNT signaling during lung development.
Published: March, 2014

Abstract: BACKGROUND: The high-mobility-group (HMG) proteins are the most abundant non-histone chromatin-associated proteins. HMG proteins are present at high levels in various undifferentiated tissues during embryonic development and their levels are stron...
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Large-scale analysis of tandem repeat variability in the human genome.
Published: March, 2014

Abstract: Tandem repeats are short DNA sequences that are repeated head-to-tail with a propensity to be variable. They constitute a significant proportion of the human genome, also occurring within coding and regulatory regions. Variation in these repeats c...
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Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.
Published: March, 2014

Abstract: BACKGROUND: Deregulation of canonical Wnt/CTNNB1 (beta-catenin) pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, w...
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PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2.
Published: March, 2014

Abstract: Development of the cerebral cortex is controlled by growth factors among which transforming growth factor beta (TGFβ) and insulin-like growth factor 1 (IGF1) have a central role. The TGFβ- and IGF1-pathways cross-talk and share signalling molecule...
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Fine mapping of genome activation in bovine embryos by RNA sequencing.
Published: March, 2014

Abstract: During maternal-to-embryonic transition control of embryonic development gradually switches from maternal RNAs and proteins stored in the oocyte to gene products generated after embryonic genome activation (EGA). Detailed insight into the onset of...
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Synthesis of multifunctional lipid–polymer conjugates: application to the elaboration of bright far-red fluorescent lipid probes
Published: March, 2014

Abstract: A new class of lipid-ended polymer conjugates presenting reactive sites regularly distributed along the polymer chain were synthesized using RAFT polymerization. The chosen modular approach enables preparation of different lipid families by tuning...
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Hook is an adapter that coordinates kinesin-3 and dynein cargo attachment on early endosomes.
Published: March, 2014

Abstract: Bidirectional membrane trafficking along microtubules is mediated by kinesin-1, kinesin-3, and dynein. Several organelle-bound adapters for kinesin-1 and dynein have been reported that orchestrate their opposing activity. However, the coordination...
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The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis.
Published: March, 2014

Abstract: The disruption of the NRF2 (nuclear factor erythroid-derived 2-like 2)/glutathione-mediated antioxidant defense pathway is a critical step in the pathogenesis of several chronic pulmonary diseases and cancer. While the mechanism of NRF2 activation...
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MBD5 and MBD6 interact with the human PR-DUB complex through their methyl-CpG-binding domain.
Published: March, 2014

Abstract: MBD5 and MBD6 are two members of the methyl-CpG-binding domain (MBD) family of proteins that are poorly characterized. Studies performed thus far have failed to show binding of the MBD5 and MBD6 MBD to methylated DNA. Here, we show that both MBD5 ...
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Counteracting Activities of OCT4 and KLF4 during Reprogramming to Pluripotency.
Published: March, 2014

Abstract: Differentiated cells can be reprogrammed into induced pluripotent stem cells (iPSCs) after overexpressing four transcription factors, of which Oct4 is essential. To elucidate the role of Oct4 during reprogramming, we investigated the immediate tra...
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Sequence capture using PCR-generated probes: a cost-effective method of targeted high-throughput sequencing for nonmodel organisms.
Published: March, 2014

Abstract: Recent advances in high-throughput sequencing library preparation and subgenomic enrichment methods have opened new avenues for population genetics and phylogenetics of nonmodel organisms. To multiplex large numbers of indexed samples while sequen...
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Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.
Published: March, 2014

Abstract: To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression qua...
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Citrullination regulates pluripotency and histone H1 binding to chromatin.
Published: March, 2014

Abstract: Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried o...
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RNAi screen in Drosophila larvae identifies histone deacetylase 3 as a positive regulator of the hsp70 heat shock gene expression during heat shock.
Published: March, 2014

Abstract: The transcription regulation of the Drosophila hsp70 gene is a complex process that involves the regulation of multiple steps, including the establishment of paused Pol II and release of Pol II into elongation upon heat shock activation. While the...
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β-agonists selectively modulate proinflammatory gene expression in skeletal muscle cells via non-canonical nuclear crosstalk mechanisms.
Published: March, 2014

Abstract: The proinflammatory cytokine Tumour Necrosis Factor (TNF)-α is implicated in a variety of skeletal muscle pathologies. Here, we have investigated how in vitro cotreatment of skeletal muscle C2C12 cells with β-agonists modulates the TNF-α-induced i...
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The transcription factor CREB has no non-redundant functions in hepatic glucose metabolism in mice.
Published: March, 2014

Abstract: AIMS/HYPOTHESIS: Excessive hepatic glucose production is a hallmark of insulin resistance in type 2 diabetes. The cAMP responsive transcription factor cAMP responsive element binding protein (CREB), thought to be a key activator of the hepatic glu...
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Polycomb binding precedes early-life stress responsive DNA methylation at the Avp enhancer.
Published: March, 2014

Abstract: Early-life stress (ELS) in mice causes sustained hypomethylation at the downstream Avp enhancer, subsequent overexpression of hypothalamic Avp and increased stress responsivity. The sequence of events leading to Avp enhancer methylation is present...
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A lipid-mediated conformational switch modulates the thermosensing activity of DesK.
Published: March, 2014

Abstract: The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK ...
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mMAPS: a flow-proteometric technique to analyze protein-protein interactions in individual signaling complexes.
Published: March, 2014

Abstract: Signal transduction is a dynamic process that regulates cellular functions through multiple types of biomolecular interactions, such as the interactions between proteins and between proteins and nucleic acids. However, the techniques currently ava...
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Cyclin-dependent kinase inhibitor 2B regulates efferocytosis and atherosclerosis.
Published: March, 2014

Abstract: Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this ...
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Contesting the dogma of an age-related heat shock response impairment: implications for cardiac-specific age-related disorders.
Published: March, 2014

Abstract: Ageing is associated with the reduced performance of physiological processes and has been proposed as a major risk factor for disease. An age-related decline in stress response pathways has been widely documented in lower organisms. In particular,...
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Peroxisome proliferator-activated receptor γ and C/EBPα synergistically activate key metabolic adipocyte genes by assisted loading.
Published: March, 2014

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) are key activators of adipogenesis. They mutually induce the expression of each other and have been reported to cooperate in...
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Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei.
Published: March, 2014

Abstract: Monoallelic expression within a gene family is found in pathogens exhibiting antigenic variation and in mammalian olfactory neurons. Trypanosoma brucei, a lethal parasite living in the human bloodstream, expresses variant surface glycoprotein (VSG...
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Identification of HilD-regulated genes in Salmonella enterica serovar Typhimurium.
Published: March, 2014

Abstract: Salmonella enterica serovar Typhimurium (S. Typhimurium) pathogenicity island 1 (SPI-1) encodes a type III secretion system required for invasion of host gut epithelial cells. Expression of SPI-1 virulence genes is controlled by a complex hierarch...
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SH2B1β interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation.
Published: March, 2014

Abstract: Neurite outgrowth is an essential process during neuronal differentiation as well as neuroregeneration. Thus, understanding the molecular and cellular control of neurite outgrowth will benefit patients with neurological diseases. We have previousl...
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Telomere repeat binding proteins are functional components of Arabidopsis telomeres and interact with telomerase.
Published: March, 2014

Abstract: Although telomere-binding proteins constitute an essential part of telomeres, in vivo data indicating the existence of a structure similar to mammalian shelterin complex in plants are limited. Partial characterization of a number of candidate prot...
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Decreased genetic dosage of hepatic yin yang 1 causes diabetic-like symptoms.
Published: March, 2014

Abstract: Insulin sensitivity in liver is characterized by the ability of insulin to efficiently inhibit glucose production and fatty acid oxidation as well as promote de novo lipid biosynthesis. Specific dysregulation of glucose and lipid metabolism in liv...
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Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.
Published: March, 2014

Abstract: Natural killer cells belong to the family of innate lymphoid cells comprising the frontline defense against infected and transformed cells. Development and activation of natural killer cells is highly dependent on interleukin-15 signaling. However...
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Sequential adaptive introgression of the mitochondrial genome in Drosophila yakuba and Drosophila santomea.
Published: March, 2014

Abstract: Interspecific hybridization provides the unique opportunity for species to tap into genetic variation present in a closely related species and potentially take advantage of beneficial alleles. It has become increasingly clear that when hybridizati...
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The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
Published: March, 2014

Abstract: The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activi...
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Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells.
Published: March, 2014

Abstract: Mass spectrometry (MS)-based proteomics typically employs multistep sample-preparation workflows that are subject to sample contamination and loss. We report an in-StageTip method for performing sample processing, from cell lysis through elution o...
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Stage-specific control of early B cell development by the transcription factor Ikaros.
Published: March, 2014

Abstract: The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant...
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FoxA1 directs the lineage and immunosuppressive properties of a novel regulatory T cell population in EAE and MS.
Published: March, 2014

Abstract: The defective generation or function of regulatory T (Treg) cells in autoimmune disease contributes to chronic inflammation and tissue injury. We report the identification of FoxA1 as a transcription factor in T cells that, after ectopic expressio...
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Centromeric histone H2B monoubiquitination promotes noncoding transcription and chromatin integrity.
Published: March, 2014

Abstract: Functional centromeres are essential for proper cell division. Centromeres are established largely by epigenetic processes resulting in incorporation of the histone H3 variant CENP-A. Here, we demonstrate the direct involvement of H2B monoubiquiti...
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The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma.
Published: March, 2014

Abstract: Pancreatic ductal adenocarcinoma (PDA) develops through distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, genetic features resulting in IPMN-associated ...
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Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components.
Published: March, 2014

Abstract: To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use nascent chromatin capture ...
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Sequencing and assembly of the 22-gb loblolly pine genome.
Published: March, 2014

Abstract: Conifers are the predominant gymnosperm. The size and complexity of their genomes has presented formidable technical challenges for whole-genome shotgun sequencing and assembly. We employed novel strategies that allowed us to determine the lobloll...
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BMP4 promotes EMT and mesodermal commitment in human embryonic stem cells via SLUG and MSX2.
Published: March, 2014

Abstract: Bone morphogenetic proteins (BMPs) initiate differentiation in human embryonic stem cells (hESCs) but the exact mechanisms have not been fully elucidated. We demonstrate here that SLUG and MSX2, transcription factors involved in epithelial-mesench...
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Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.
Published: March, 2014

Abstract: Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its o...
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PGC7 suppresses TET3 for protecting DNA methylation.
Published: March, 2014

Abstract: Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or ...
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Characterization of two different Asf1 histone chaperones with distinct cellular localizations and functions in Trypanosoma brucei.
Published: March, 2014

Abstract: The anti-silencing function protein 1 (Asf1) is a chaperone that forms a complex with histones H3 and H4 facilitating dimer deposition and removal from chromatin. Most eukaryotes possess two different Asf1 chaperones but their specific functions a...
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The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen-receptor positive tumors.
Published: March, 2014

Abstract: Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particula...
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A recently evolved class of alternative 3'-terminal exons involved in cell cycle regulation by topoisomerase inhibitors.
Published: February, 2014

Abstract: Alternative 3'-terminal exons, which use intronic polyadenylation sites, are generally less conserved and expressed at lower levels than the last exon of genes. Here we discover a class of human genes, in which the last exon appeared recently duri...
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Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity.
Published: February, 2014

Abstract: Cells differentiate when transcription factors bind accessible cis-regulatory elements to establish specific gene expression programs. In differentiating embryonic stem cells, chromatin at lineage-restricted genes becomes sequentially accessible, ...
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Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.
Published: February, 2014

Abstract: Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not furth...
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Maintenance of Heterochromatin Boundary and Nucleosome Composition at Promoters by the Asf1 Histone Chaperone and SWR1-C Chromatin Remodeler in Saccharomyces cerevisiae.
Published: February, 2014

Abstract: Chromatin remodeling complexes cooperate to regulate gene promoters and to define chromatin neighborhoods. Here, we identified genetic and functional connections between two silencing-related chromatin factors in the maintenance of native heteroch...
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Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice.
Published: February, 2014

Abstract: "Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model...
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Sequencing-based large-scale genomics approaches with small numbers of isolated maize meiocytes.
Published: February, 2014

Abstract: High-throughput sequencing has become the large-scale approach of choice to study global gene expression and the distribution of specific chromatin marks and features. However, the limited availability of large amounts of purified cells made it ve...
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Reversible Top1 cleavage complexes are stabilized strand-specifically at the ribosomal replication fork barrier and contribute to ribosomal DNA stability.
Published: February, 2014

Abstract: Various topological constraints at the ribosomal DNA (rDNA) locus impose an extra challenge for transcription and DNA replication, generating constant torsional DNA stress. The topoisomerase Top1 is known to release such torsion by single-strand n...
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The FOS transcription factor family differentially controls trophoblast migration and invasion.
Published: February, 2014

Abstract: Extravillous trophoblast invasion is a fundamental component of human placentation. Invading trophoblast cells promote blood flow to the conceptus by actively remodeling the uterine vasculature. The extent of trophoblast invasion is tightly regula...
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Myc and max genome-wide binding sites analysis links the Myc regulatory network with the polycomb and the core pluripotency networks in mouse embryonic stem cells.
Published: February, 2014

Abstract: Myc is a master transcription factor that has been demonstrated to be required for embryonic stem cell (ESC) pluripotency, self-renewal, and inhibition of differentiation. Although recent works have identified several Myc-targets in ESCs, the list...
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Geriatric muscle stem cells switch reversible quiescence into senescence.
Published: February, 2014

Abstract: Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incap...
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Runx1t1 (Runt-related transcription factor 1; translocated to, 1) epigenetically regulates the proliferation and nitric oxide production of microglia.
Published: February, 2014

Abstract: BACKGROUND: Microglia, the resident immune cells of the brain, undergo rapid proliferation and produce several proinflammatory molecules and nitric oxide (NO) when activated in neuropathological conditions. Runx1t1 (Runt-related transcription fact...
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Glial wingless/Wnt regulates glutamate receptor clustering and synaptic physiology at the Drosophila neuromuscular junction.
Published: February, 2014

Abstract: Glial cells are emerging as important regulators of synapse formation, maturation, and plasticity through the release of secreted signaling molecules. Here we use chromatin immunoprecipitation along with Drosophila genomic tiling arrays to define ...
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The long non-coding RNA Paupar regulates the expression of both local and distal genes.
Published: February, 2014

Abstract: Although some long noncoding RNAs (lncRNAs) have been shown to regulate gene expression in cis, it remains unclear whether lncRNAs can directly regulate transcription in trans by interacting with chromatin genome-wide independently of their sites ...
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Genome-wide binding patterns of thyroid hormone receptor beta.
Published: February, 2014

Abstract: Thyroid hormone (TH) receptors (TRs) play central roles in metabolism and are major targets for pharmaceutical intervention. Presently, however, there is limited information about genome wide localizations of TR binding sites. Thus, complexities o...
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Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring.
Published: February, 2014

Abstract: The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offsprin...
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CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans.
Published: February, 2014

Abstract: Cyclin-dependent kinase (CDK) plays a vital role in proliferation control across eukaryotes. Despite this, how CDK mediates cell cycle and developmental transitions in metazoa is poorly understood. In this paper, we identify orthologues of Sld2, a...
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Reduced Euchromatin histone methyltransferase 1 causes developmental delay, hypotonia, and cranial abnormalities associated with increased bone gene expression in Kleefstra syndrome mice.
Published: February, 2014

Abstract: Haploinsufficiency of Euchromatin histone methyltransferase 1 (EHMT1), a chromatin modifying enzyme, is the cause of Kleefstra syndrome (KS). KS is an intellectual disability (ID) syndrome, with general developmental delay, hypotonia, and craniofa...
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Sp1 and Sp3 transcription factors regulate the basal expression of human microsomal epoxide hydrolase (EPHX1) through interaction with the E1b far upstream promoter.
Published: February, 2014

Abstract: Microsomal epoxide hydrolase (mEH, EPHX1) is a critical biotransformation enzyme, catalyzing the metabolism of many xenobiotics. Human mEH is transcribed using alternative promoters. The upstream E1 promoter is active in liver while the far upstre...
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C/EBPα poises B cells for rapid reprogramming into induced pluripotent stem cells.
Published: February, 2014

Abstract: CCAAT/enhancer binding protein-α (C/EBPα) induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem (iPS) cells when co-expressed with the transcription factors Oct4 (Pou...
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Nonstochastic reprogramming from a privileged somatic cell state.
Published: February, 2014

Abstract: Reprogramming somatic cells to induced pluripotency by Yamanaka factors is usually slow and inefficient and is thought to be a stochastic process. We identified a privileged somatic cell state, from which acquisition of pluripotency could occur in...
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A deterministic analysis of genome integrity during neoplastic growth in Drosophila.
Published: February, 2014

Abstract: The development of cancer has been associated with the gradual acquisition of genetic alterations leading to a progressive increase in malignancy. In various cancer types this process is enabled and accelerated by genome instability. While genome ...
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Sumoylation of the THO complex regulates the biogenesis of a subset of mRNPs.
Published: February, 2014

Abstract: Assembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we dem...
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c-Myc-dependent transcriptional regulation of cell cycle and nucleosomal histones during oligodendrocyte differentiation.
Published: February, 2014

Abstract: Oligodendrocyte progenitor cells (OPCs) have the ability to divide or to growth arrest and differentiate into myelinating oligodendrocytes in the developing brain. Due to their high number and the persistence of their proliferative capacity in the...
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Hundreds of circular novel plasmids and DNA elements identified in a rat cecum metamobilome.
Published: February, 2014

Abstract: Metagenomic approaches are widespread in microbiological research, but so far, the knowledge on extrachromosomal DNA diversity and composition has largely remained dependant on cultivating host organisms. Even with the emergence of metagenomics, c...
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A Drosophila in vivo screen identifies store-operated calcium entry as a key regulator of adiposity.
Published: February, 2014

Abstract: To unravel the evolutionarily conserved genetic network underlying energy homeostasis, we performed a systematic in vivo gene knockdown screen in Drosophila. We used a transgenic RNAi library enriched for fly orthologs of human genes to functional...
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Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain.
Published: February, 2014

Abstract: DNA methylation has critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single base-resolution DNA methylome from adult mouse dentate neurons c...
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Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines.
Published: February, 2014

Abstract: The aryl hydrocarbon receptor (AhR) is an important mediator of toxic responses after exposure to xenobiotics including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like polychlorinated biphenyls (PCBs). Activation of AhR responsive genes...
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Adult glucocorticoid exposure leads to transcriptional and DNA methylation changes in nuclear steroid receptors in the hippocampus and kidney of mouse male offspring.
Published: February, 2014

Abstract: Synthetic glucocorticoids (sGCs) are commonly prescribed for the management of inflammatory and endocrine disorders. However, nothing is known regarding the effects of sGC on adult germline methylome and whether these effects can be transmitted to...
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The BAF60 Subunit of the SWI/SNF Chromatin-Remodeling Complex Directly Controls the Formation of a Gene Loop at FLOWERING LOCUS C in Arabidopsis.
Published: February, 2014

Abstract: SWI/SNF complexes mediate ATP-dependent chromatin remodeling to regulate gene expression. Many components of these complexes are evolutionarily conserved, and several subunits of Arabidopsis thaliana SWI/SNF complexes are involved in the control o...
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DSSylation, a novel protein modification targets proteins induced by oxidative stress, and facilitates their degradation in cells.
Published: February, 2014

Abstract: Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a rol...
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A cohesin-independent role for NIPBL at promoters provides insights in CdLS.
Published: February, 2014

Abstract: The cohesin complex is crucial for chromosome segregation during mitosis and has recently also been implicated in transcriptional regulation and chromatin architecture. The NIPBL protein is required for the loading of cohesin onto chromatin, but h...
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The role of plasma membrane estrogen receptors in mediating the estrogen induction of progesterone receptors in hypothalamic ventromedial neurons.
Published: February, 2014

Abstract: Progesterone is well known for its role in the modulation of sexual behavior. In the ventromedial nucleus (VMN), a part of the mediobasal hypothalamus which regulates sexual behavior in female rodents, estrogens induce the expression of progestero...
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Human RECQ5 helicase promotes repair of DNA double-strand breaks by synthesis-dependent strand annealing.
Published: February, 2014

Abstract: Most mitotic homologous recombination (HR) events proceed via a synthesis-dependent strand annealing mechanism to avoid crossing over, which may give rise to chromosomal rearrangements and loss of heterozygosity. The molecular mechanisms controlli...
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The chromatin remodeller CHD8 is required for E2F-dependent transcription activation of S-phase genes.
Published: February, 2014

Abstract: The precise regulation of S-phase-specific genes is critical for cell proliferation. How the repressive chromatin configuration mediated by the retinoblastoma protein and repressor E2F factors changes at the G1/S transition to allow transcription ...
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A highly conserved region within H2B is important for FACT to act on nucleosomes.
Published: February, 2014

Abstract: Histone N-terminal tails play crucial roles in chromatin-related processes. The tails of histones H3 and H4 are highly conserved and well characterized, but much less is known about the functions of the tails of histones H2A and H2B and their sequ...
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The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.
Published: January, 2014

Abstract: Cardiac dysfunction is the second leading cause of death in myotonic dystrophy type 1 (DM1), primarily because of arrhythmias and cardiac conduction defects. A screen of more than 500 microRNAs (miRNAs) in a DM1 mouse model identified 54 miRNAs th...
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Assembly of the genome of the disease vector Aedes aegypti onto a genetic linkage map allows mapping of genes affecting disease transmission.
Published: January, 2014

Abstract: The mosquito Aedes aegypti transmits some of the most important human arboviruses, including dengue, yellow fever and chikungunya viruses. It has a large genome containing many repetitive sequences, which has resulted in the genome being poorly as...
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ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor-initiating cell state.
Published: January, 2014

Abstract: Glioblastoma (GBM) harbors subpopulations of therapy-resistant tumor-initiating cells (TICs) that are self-renewing and multipotent. To understand the regulation of the TIC state, we performed an image-based screen for genes regulating GBM TIC mai...
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Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance.
Published: January, 2014

Abstract: RGS10 is an important regulator of cell survival and chemoresistance in ovarian cancer. We recently showed that RGS10 transcript expression is suppressed during acquired chemoresistance in ovarian cancer. The suppression of RGS10 is due to DNA hyp...
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The role of DNA methylation in regulation of the murine Lhx3 gene.
Published: January, 2014

Abstract: LHX3 is a LIM-homeodomain transcription factor with critical roles in pituitary and nervous system development. Mutations in the LHX3 gene are associated with pediatric diseases featuring severe hormone deficiencies, hearing loss, developmental de...
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A role for peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) in the regulation of cardiac mitochondrial phospholipid biosynthesis.
Published: January, 2014

Abstract: The energy demands of the adult mammalian heart are met largely by ATP generated via oxidation of fatty acids in a high capacity mitochondrial system. Peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1)-α and -β serve as inducible t...
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Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin.
Published: January, 2014

Abstract: JARID2 is an accessory component of Polycomb repressive complex-2 (PRC2) required for the differentiation of embryonic stem cells (ESCs). A role for JARID2 in the recruitment of PRC2 to target genes silenced during differentiation has been put for...
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An Easy, Convenient Cell and Tissue Extraction Protocol for Nuclear Magnetic Resonance Metabolomics.
Published: January, 2014

Abstract: INTRODUCTION: As a complement to the classic metabolomics biofluid studies, the visualisation of the metabolites contained in cells or tissues could be a very powerful tool to understand how the local metabolism and biochemical pathways could be a...
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Suppression of UV-B stress responses by flg22 is regulated at the chromatin level via histone modification.
Published: January, 2014

Abstract: Genes of the flavonol pathway are activated by UV-B, but suppressed by concomitant flg22 application in Arabidopsis. Analysis at the metabolite level suggested that this regulation allows the plant to focus its secondary metabolism on the plant de...
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Lysine-specific demethylase 1 regulates differentiation onset and migration of trophoblast stem cells.
Published: January, 2014

Abstract: Propagation and differentiation of stem cell populations are tightly regulated to provide sufficient cell numbers for tissue formation while maintaining the stem cell pool. Embryonic parts of the mammalian placenta are generated from differentiati...
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Lysine deacetylase inhibition prevents diabetes by chromatin-independent immunoregulation and β-cell protection.
Published: January, 2014

Abstract: Type 1 diabetes is due to destruction of pancreatic β-cells. Lysine deacetylase inhibitors (KDACi) protect β-cells from inflammatory destruction in vitro and are promising immunomodulators. Here we demonstrate that the clinically well-tolerated KD...
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Structural basis for the inhibition of the chromatin repressor BAHD1 by the bacterial nucleomodulin LntA.
Published: January, 2014

Abstract: UNLABELLED: The nucleus has emerged as a key target for nucleomodulins, a family of effectors produced by bacterial pathogens to control host transcription or other nuclear processes. The virulence factor LntA from Listeria monocytogenes stimulate...
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Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.
Published: January, 2014

Abstract: Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while induci...
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Peroxisome proliferator-activated receptor γ regulates genes involved in insulin/insulin-like growth factor signaling and lipid metabolism during adipogenesis through functionally distinct enhancer classes.
Published: January, 2014

Abstract: The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is a transcription factor whose expression is induced during adipogenesis and that is required for the acquisition and control of mature adipocyte functions. Indeed, PPAR induc...
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SPBP is a sulforaphane induced transcriptional coactivator of NRF2 regulating expression of the autophagy receptor p62/SQSTM1.
Published: January, 2014

Abstract: Organisms exposed to oxidative stress respond by orchestrating a stress response to prevent further damage. Intracellular levels of antioxidant agents increase, and damaged components are removed by autophagy induction. The KEAP1-NRF2 signaling pa...
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Depletion of sirtuin 1 (SIRT1) leads to epigenetic modifications of telomerase (TERT) gene in hepatocellular carcinoma cells.
Published: January, 2014

Abstract: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telome...
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mRNA levels of related Abcb genes change opposite to each other upon histone deacetylase inhibition in drug-resistant rat hepatoma cells.
Published: January, 2014

Abstract: The multidrug-resistant phenotype of tumor cells is acquired via an increased capability of drug efflux by ABC transporters and causes serious problems in cancer treatment. With the aim to uncover whether changes induced by epigenetic mechanisms i...
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DUSP1 is a novel target for enhancing pancreatic cancer cell sensitivity to gemcitabine.
Published: January, 2014

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with a poor prognosis that is characterized by excessive mitogenic pathway activation and marked chemoresistance to a broad spectrum of chemotherapeutic drugs. Dual specificity protein pho...
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The thyroid hormone receptor β induces DNA damage and premature senescence.
Published: January, 2014

Abstract: There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribo...
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A role for FACT in repopulation of nucleosomes at inducible genes.
Published: January, 2014

Abstract: Xenobiotic drugs induce Pleiotropic Drug Resistance (PDR) genes via the orthologous Pdr1/Pdr3 transcription activators. We previously identified the Mediator transcription co-activator complex as a key target of Pdr1 orthologs and demonstrated tha...
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Mutations in POGLUT1, encoding protein O-glucosyltransferase 1, cause autosomal-dominant Dowling-Degos disease.
Published: January, 2014

Abstract: Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic muta...
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CLOCK:BMAL1 is a pioneer-like transcription factor.
Published: January, 2014

Abstract: The mammalian circadian clock relies on the master genes CLOCK and BMAL1 to drive rhythmic gene expression and regulate biological functions under circadian control. Here we show that rhythmic CLOCK:BMAL1 DNA binding promotes rhythmic chromatin op...
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Integrated transcriptome analysis of mouse spermatogenesis.
Published: January, 2014

Abstract: BACKGROUND: Differentiation of primordial germ cells into mature spermatozoa proceeds through multiple stages, one of the most important of which is meiosis. Meiotic recombination is in turn a key part of meiosis. To achieve the highly specialized...
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The genome-wide landscape of DNA methylation and hydroxymethylation in response to sleep deprivation impacts on synaptic plasticity genes.
Published: January, 2014

Abstract: Sleep is critical for normal brain function and mental health. However, the molecular mechanisms mediating the impact of sleep loss on both cognition and the sleep electroencephalogram remain mostly unknown. Acute sleep loss impacts brain gene exp...
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Genome-wide profiling of transcription factor binding and epigenetic marks in adipocytes by ChIP-seq.
Published: January, 2014

Abstract: The recent advances in high-throughput sequencing combined with various other technologies have allowed detailed and genome-wide insight into the transcriptional networks that control adipogenesis. Chromatin immunoprecipitation (ChIP) combined wit...
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Genome-wide data (ChIP-seq) enabled identification of cell wall-related and aquaporin genes as targets of tomato ASR1, a drought stress-responsive transcription factor.
Published: January, 2014

Abstract: BACKGROUND: Identifying the target genes of transcription factors is important for unraveling regulatory networks in all types of organisms. Our interest was precisely to uncover the spectrum of loci regulated by a widespread plant transcription f...
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Analyzing the functions and structure of the human lipodystrophy protein seipin.
Published: January, 2014

Abstract: Disruption of the gene BSCL2, which encodes the protein seipin, causes severe generalized lipodystrophy in humans with a near complete absence of adipose tissue. Moreover, cell culture studies have demonstrated that seipin plays a critical cell-au...
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Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants.
Published: January, 2014

Abstract: BACKGROUND: The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW,
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Differential methylation of the TRPA1 promoter in pain sensitivity.
Published: January, 2014

Abstract: Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further ...
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Negative regulation of the peptidylarginine deiminase type IV promoter by NF-κB in human myeloid cells.
Published: January, 2014

Abstract: High titers of anti-citrullinated protein/peptide antibodies (ACPAs) have been detected in sera of rheumatoid arthritis (RA) patients, implicating citrullinating enzymes in the pathogenesis of RA. Peptidylarginine deiminase type IV (PAD4) is a mem...
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Differential expression of histone H3 genes and selective association of the variant H3.7 with a specific sequence class in Stylonychia macronuclear development.
Published: January, 2014

Abstract: BACKGROUND: Regulation of chromatin structure involves deposition of selective histone variants into nucleosome arrays. Numerous histone H3 variants become differentially expressed by individual nanochromosomes in the course of macronuclear differ...
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Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice.
Published: January, 2014

Abstract: BACKGROUND: Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymet...
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Viral aetiology influenza like illnesses in Santa Cruz, Bolivia (2010-2012).
Published: January, 2014

Abstract: BACKGROUND: Acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of Influenza Like Illnesses (ILIs) remain largely unknown in developing countries. This study represents the first attempt to ch...
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Strand-specific RNA-Seq reveals widespread and developmentally regulated transcription of natural antisense transcripts in Plasmodium falciparum.
Published: January, 2014

Abstract: BACKGROUND: Advances in high-throughput sequencing have led to the discovery of widespread transcription of natural antisense transcripts (NATs) in a large number of organisms, where these transcripts have been shown to play important roles in the...
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Histone Deacetylase inhibition with Valproic Acid down-regulates Osteocalcin gene expression in Human Dental Pulp Stem Cells and Osteoblasts: Evidence for HDAC2 involvement.
Published: January, 2014

Abstract: Adult mesenchymal stem cells, such as dental pulp stem cells, are of great interest for cell-based tissue engineering strategies because they can differentiate into a variety of tissue-specific cells, above all, into osteoblasts. In recent years, ...
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Histone Deacetylase Classes I and II Regulate Kaposi's Sarcoma-Associated Herpesvirus Reactivation.
Published: January, 2014

Abstract: In primary effusion lymphoma (PEL) cells infected with latent Kaposi's sarcoma-associated herpesvirus (KSHV), the promoter of the viral lytic switch gene, Rta, is organized into bivalent chromatin, similar to cellular developmental switch genes. H...
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Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.
Published: January, 2014

Abstract: The contribution of cis-regulatory mutations to human disease remains poorly understood. Whole-genome sequencing can identify all noncoding variants, yet the discrimination of causal regulatory mutations represents a formidable challenge. We used ...
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Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb.
Published: January, 2014

Abstract: Meis homeodomain transcription factors control cell proliferation, cell fate specification and differentiation in development and disease. Previous studies have largely focused on Meis contribution to the development of non-neuronal tissues. By co...
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Regulation of the neuronal transcription factor NPAS4 by REST and microRNAs.
Published: January, 2014

Abstract: NPAS4 is a brain restricted, activity-induced transcription factor which regulates the expression of inhibitory synapse genes to control homeostatic excitatory/inhibitory balance in neurons. NPAS4 is required for normal social interaction and cont...
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Human cytomegalovirus major immediate early 1 protein targets host chromosomes by docking to the acidic pocket on the nucleosome surface.
Published: January, 2014

Abstract: The 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechan...
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Large conserved domains of low DNA methylation maintained by Dnmt3a.
Published: January, 2014

Abstract: Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into the mechanisms that promote shifts in DNA methylation and contribute to changes in cell fate, including malignant transformation, we performed...
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Inactivating CUX1 mutations promote tumorigenesis.
Published: January, 2014

Abstract: A major challenge in cancer genetics is to determine which low-frequency somatic mutations are drivers of tumorigenesis. Here we interrogate the genomes of 7,651 diverse human cancers and find inactivating mutations in the homeodomain transcriptio...
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Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid.
Published: December, 2013

Abstract: A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The m...
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Molecular mechanisms of regulation and action of microRNA-199a in testicular germ cell tumor and glioblastomas.
Published: December, 2013

Abstract: MicroRNA-199a (miRNA-199a) has been shown to have comprehensive functions and behave differently in different systems and diseases. It is encoded by two loci in the human genome, miR-199a-1 in chromosome 19 and miR-199a-2 in chromosome 1. Both loc...
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Anti-androgen resistance in prostate cancer cells chronically induced by interleukin-1β
Published: December, 2013

Abstract: Chronic inflammation has been linked to cancer initiation and progression in a variety of tissues, yet the impact of acute and chronic inflammatory signaling on androgen receptor function has not been widely studied. In this report, we examine the...
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Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus.
Published: December, 2013

Abstract: BCL6 is a zinc-finger transcriptional repressor, which is highly expressed in germinal centre B-cells and is essential for germinal centre formation and T-dependent antibody responses. Constitutive BCL6 expression is sufficient to produce lymphoma...
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Rapid and pervasive changes in genome-wide enhancer usage during mammalian development.
Published: December, 2013

Abstract: Enhancers are distal regulatory elements that can activate tissue-specific gene expression and are abundant throughout mammalian genomes. Although substantial progress has been made toward genome-wide annotation of mammalian enhancers, their tempo...
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Prmt7 is dispensable in tissue culture models for adipogenic differentiation
Published: December, 2013

Abstract: Protein arginine methylation is a common posttranslational modification that has been implicated in numerous biological processes including gene expression. The mammalian genome encodes nine protein arginine methyltransferases (Prmts) that catalyz...
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H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1.
Published: December, 2013

Abstract: The H19 gene controls the expression of several genes within the Imprinted Gene Network (IGN), involved in growth control of the embryo. However, the underlying mechanisms of this control remain elusive. Here, we identified the methyl-CpG-binding ...
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Nfatc1 orchestrates aging in hair follicle stem cells.
Published: December, 2013

Abstract: Hair production is fueled by stem cells (SCs), which transition between cyclical bouts of rest and activity. Here, we explore why hair growth wanes with age. We show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and abbrevia...
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Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks.
Published: December, 2013

Abstract: Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation rem...
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UTX coordinates steroid hormone-mediated autophagy and cell death.
Published: December, 2013

Abstract: Correct spatial and temporal induction of numerous cell type-specific genes during development requires regulated removal of the repressive histone H3 lysine 27 trimethylation (H3K27me3) modification. Here we show that the H3K27me3 demethylase dUT...
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Local depletion of DNA methylation identifies a repressive p53 regulatory region in the NEK2 promoter.
Published: December, 2013

Abstract: Genome-scale mapping suggests that the function of DNA methylation varies with genomic context beyond transcriptional repression. However, the use of DNA-demethylating agents (e.g. 5-aza-2'-deoxycytidine (5aza-dC)) to study epigenetic regulation o...
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miR-16 and miR-26a target checkpoint kinases Wee1 and Chk1 in response to p53 activation by genotoxic stress.
Published: December, 2013

Abstract: The tumour suppressor p53 is a crucial regulator of cell cycle arrest and apoptosis by acting as a transcription factor to regulate a variety of genes. At least in part, this control is exerted by p53 via regulating expression of numerous microRNA...
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p53 status determines the role of autophagy in pancreatic tumour development.
Published: December, 2013

Abstract: Macroautophagy (hereafter referred to as autophagy) is a process in which organelles termed autophagosomes deliver cytoplasmic constituents to lysosomes for degradation. Autophagy has a major role in cellular homeostasis and has been implicated in...
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β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications.
Published: December, 2013

Abstract: Increasing evidence points to nuclear compartmentalization as a contributing mechanism for gene regulation, yet mechanisms for compartmentalization remain unclear. In this paper, we use autonomous targeting of bacterial artificial chromosome (BAC)...
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The maize glossy13 gene, cloned via BSR-Seq and Seq-walking encodes a putative ABC transporter required for the normal accumulation of epicuticular waxes.
Published: December, 2013

Abstract: Aerial plant surfaces are covered by epicuticular waxes that among other purposes serve to control water loss. Maize glossy mutants originally identified by their "glossy" phenotypes exhibit alterations in the accumulation of epicuticular waxes. B...
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Oncogenic K-Ras and loss of Smad4 mediate invasion by activating an EGFR/NF-κB Axis that induces expression of MMP9 and uPA in human pancreas progenitor cells.
Published: December, 2013

Abstract: Activating K-Ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). To further study the individual and combinatorial roles of...
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Reprogramming of lysosomal gene expression by interleukin-4 and Stat6
Published: December, 2013

Abstract: Background Lysosomes play important roles in multiple aspects of physiology, but the problem of how the transcription of lysosomal genes is coordinated remains incompletely understood. The goal of this study was to illuminate the physiological c...
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The role of Ctk1 kinase in termination of small non-coding RNAs.
Published: December, 2013

Abstract: Transcription termination in Saccharomyces cerevisiae can be performed by at least two distinct pathways and is influenced by the phosphorylation status of the carboxy-terminal domain (CTD) of RNA polymerase II (Pol II). Late termination of mRNAs ...
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Transcriptional activation of Mina by Sp1/3 factors.
Published: December, 2013

Abstract: Mina is an epigenetic gene regulatory protein known to function in multiple physiological and pathological contexts, including pulmonary inflammation, cell proliferation, cancer and immunity. We showed previously that the level of Mina gene expres...
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ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia.
Published: December, 2013

Abstract: Acute myeloid leukemia (AML) is frequently linked to epigenetic abnormalities and deregulation of gene transcription, which lead to aberrant cell proliferation and accumulation of undifferentiated precursors. ZRF1, a recently characterized epigene...
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Distinctive patterns of epigenetic marks are associated with promoter regions of mouse LINE-1 and LTR retrotransposons.
Published: December, 2013

Abstract: BACKGROUND: The long terminal repeat (LTR) retrotransposons and the non-LTR retrotransposons (LINE-1 or L1) make up more than one-third of the mouse genome. Because of their abundance, the retrotransposons are the major players in genomic structur...
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Elevated levels of FOXA1 facilitate androgen receptor chromatin binding resulting in a CRPC-like phenotype.
Published: December, 2013

Abstract: Castration-resistant prostate cancer (CRPC) continues to pose a significant clinical challenge with new generation second-line hormonal therapies affording limited improvement in disease outcome. As the androgen receptor (AR) remains a critical dr...
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Transcription factor occupancy can mediate active turnover of DNA methylation at regulatory regions.
Published: December, 2013

Abstract: Distal regulatory elements, including enhancers, play a critical role in regulating gene activity. Transcription factor binding to these elements correlates with Low Methylated Regions (LMRs) in a process that is poorly understood. Here we ask whe...
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The PAF complex and Prf1/Rtf1 delineate distinct Cdk9-dependent pathways regulating transcription elongation in fission yeast.
Published: December, 2013

Abstract: Cyclin-dependent kinase 9 (Cdk9) promotes elongation by RNA polymerase II (RNAPII), mRNA processing, and co-transcriptional histone modification. Cdk9 phosphorylates multiple targets, including the conserved RNAPII elongation factor Spt5 and RNAPI...
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Rapid Transposon Liquid Enrichment Sequencing (TnLE-seq) for Gene Fitness Evaluation in Underdeveloped Bacterial Systems.
Published: December, 2013

Abstract: Whole-genome fitness analysis in microbes that uses saturating transposon mutagenesis combined with massively parallel sequencing (Tn-seq) is providing a measure of the contribution of each gene to a given growth condition. With this technique, ge...
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Alternative End-Joining and Classical Nonhomologous End-Joining Pathways Repair Different Types of Double-Strand Breaks during Class-Switch Recombination.
Published: December, 2013

Abstract: Classical nonhomologous end-joining (C-NHEJ) and alternative end-joining (A-EJ) are the main DNA double-strand break (DSB) repair pathways when a sister chromatid is not available. However, it is not clear how one pathway is chosen over the other ...
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Two Histone Deacetylases, FfHda1 and FfHda2, Are Important for Fusarium fujikuroi Secondary Metabolism and Virulence.
Published: December, 2013

Abstract: Histone modifications are crucial for the regulation of secondary metabolism in various filamentous fungi. Here we studied the involvement of histone deacetylases (HDACs) in secondary metabolism in the phytopathogenic fungus Fusarium fujikuroi, a ...
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Genome-wide chromatin analysis in mature mouse and human spermatozoa.
Published: December, 2013

Abstract: At the end of mammalian spermatogenesis, chromatin in differentiating germ cells is extensively remodeled, with the majority of nucleosomes being removed and ultimately exchanged by highly basic proteins named protamines. Residual nucleosomes are,...
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The microRNA miR-433 promotes renal fibrosis by amplifying the TGF-β/Smad3-Azin1 pathway.
Published: December, 2013

Abstract: The TGF-β/Smad3 pathway plays a major role in tissue fibrosis, but the precise mechanisms are not fully understood. Here we identified microRNA miR-433 as an important component of TGF-β/Smad3-driven renal fibrosis. The miR-433 was upregulated fol...
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Mediator links transcription and DNA repair by facilitating Rad2/XPG recruitment.
Published: December, 2013

Abstract: Mediator is a large multiprotein complex conserved in all eukaryotes. The crucial function of Mediator in transcription is now largely established. However, we found that this complex also plays an important role by connecting transcription with D...
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Oral administration of transforming growth factor-β1 (TGF-β1) protects the immature gut from injury via Smad protein-dependent suppression of epithelial nuclear factor κB (NF-κB) signaling and proinflammatory cytokine production.
Published: November, 2013

Abstract: Inflammatory immune responses play an important role in mucosal homeostasis and gut diseases. Nuclear factor κB (NF-κB), central to the proinflammatory cascade, is activated in necrotizing enterocolitis (NEC), a devastating condition of intestinal...
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BORIS/CTCFL is an RNA-binding protein that associates with polysomes.
Published: November, 2013

Abstract: BACKGROUND: BORIS (CTCFL), a paralogue of the multifunctional and ubiquitously expressed transcription factor CTCF, is best known for its role in transcriptional regulation. In the nucleus, BORIS is particularly enriched in the nucleolus, a crucia...
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A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice.
Published: November, 2013

Abstract: Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly ...
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Toxoplasma gondii inhibits IFN-γ- and IFN-β-induced host cell STAT1 transcriptional activity by increasing the association of STAT1 with DNA.
Published: November, 2013

Abstract: The IFN-γ response, mediated by the STAT1 transcription factor, is crucial for host defense against the intracellular pathogen Toxoplasma gondii, but prior infection with Toxoplasma can inhibit this response. Recently it was reported that th...
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A quantitative telomeric chromatin isolation protocol identifies different telomeric states.
Published: November, 2013

Abstract: Telomere composition changes during tumourigenesis, aging and in telomere syndromes in a poorly defined manner. Here we develop a quantitative telomeric chromatin isolation protocol (QTIP) for human cells, in which chromatin is cross-linked, immun...
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Reactive Oxygen Species Induce Epigenetic Instability through the Formation of 8-Hydroxydeoxyguanosine in Human Hepatocarcinogenesis.
Published: November, 2013

Abstract: Chronic hepatitis C (CHC) triggers oxidative stress and contributes to the emergence of hepatocellular carcinoma (HCC). We previously reported that tumor suppressor gene (TSG) methylation is a critical factor during the early stages of hepatocarci...
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The nuclear receptor Rev-erbα controls circadian thermogenic plasticity.
Published: November, 2013

Abstract: Circadian oscillation of body temperature is a basic, evolutionarily conserved feature of mammalian biology. In addition, homeostatic pathways allow organisms to protect their core temperatures in response to cold exposure. However, the mechanism ...
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Transcriptome surveillance by selective termination of noncoding RNA synthesis.
Published: November, 2013

Abstract: Pervasive transcription of eukaryotic genomes stems to a large extent from bidirectional promoters that synthesize mRNA and divergent noncoding RNA (ncRNA). Here, we show that ncRNA transcription in the yeast S. cerevisiae is globally restricted b...
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Suggestive linkage of familial mesial temporal lobe epilepsy to chromosome 3q26.
Published: November, 2013

Abstract: PURPOSE: To describe the clinical findings in a family with a benign form of mesial temporal lobe epilepsy and to identify the causative genetic factors. METHODS: All participants were personally interviewed and underwent neurologic examination. T...
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PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin.
Published: November, 2013

Abstract: PRH/HHex (proline-rich homeodomain protein) is a transcription factor that controls cell proliferation and cell differentiation in a variety of tissues. Aberrant subcellular localisation of PRH is associated with breast cancer and thyroid cancer. ...
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Pluripotency factors and Polycomb Group proteins repress aryl hydrocarbon receptor expression in murine embryonic stem cells.
Published: November, 2013

Abstract: The aryl hydrocarbon receptor (AHR) is a transcription factor and environmental sensor that regulates expression of genes involved in drug-metabolism and cell cycle regulation. Chromatin immunoprecipitation analyses, Ahr ablation in mice and studi...
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Adenovirus precursor pVII protein stability is regulated by its propeptide sequence.
Published: November, 2013

Abstract: Adenovirus encodes for the pVII protein, which interacts and modulates virus DNA structure in the infected cells. The pVII protein is synthesized as the precursor protein and undergoes proteolytic processing by viral proteinase Avp, leading to rel...
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Structural variation-associated expression changes are paralleled by chromatin architecture modifications.
Published: November, 2013

Abstract: UNLABELLED: Copy number variants (CNVs) influence the expression of genes that map not only within the rearrangement, but also to its flanks. To assess the possible mechanism(s) underlying this "neighboring effect", we compared intrachromosomal in...
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Drosophila UTX Coordinates with p53 to Regulate ku80 Expression in Response to DNA Damage.
Published: November, 2013

Abstract: UTX is known as a general factor that activates gene transcription during development. Here, we demonstrate an additional essential role of UTX in the DNA damage response, in which it upregulates the expression of ku80 in Drosophila, both in cultu...
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Frequent alteration of the protein synthesis of enzymes for glucose metabolism in hepatocellular carcinomas.
Published: November, 2013

Abstract: BACKGROUND: Cancer cells show enhanced glycolysis and inhibition of oxidative phosphorylation, even in the presence of sufficient oxygen (aerobic glycolysis). Glycolysis is much less efficient for energy production than oxidative phosphorylation, ...
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Comparative analysis of affinity-based 5-hydroxymethylation enrichment techniques.
Published: November, 2013

Abstract: The epigenetic modification of 5-hydroxymethylcytosine (5hmC) is receiving great attention due to its potential role in DNA methylation reprogramming and as a cell state identifier. Given this interest, it is important to identify reliable and cos...
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High-resolution microbial community reconstruction by integrating short reads from multiple 16S rRNA regions.
Published: November, 2013

Abstract: The emergence of massively parallel sequencing technology has revolutionized microbial profiling, allowing the unprecedented comparison of microbial diversity across time and space in a wide range of host-associated and environmental ecosystems. A...
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MAP Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7.
Published: November, 2013

Abstract: Cbx7 is one of five mammalian orthologs of the Drosophila Polycomb (Pc). Cbx7 recognizes methylated lysine residues on the histone H3 tail and contributes to gene silencing in the context of the Polycomb Repressive Complex 1 (PRC1). However, our k...
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Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network.
Published: November, 2013

Abstract: Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analy...
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Insulin-dependent transcriptional control in L6 rat myotubes is associated with modulation of histone acetylation and accumulation of the histone variant H2A.Z in the proximity of the transcriptional start site
Published: November, 2013

Abstract: Besides its direct metabolic effects, insulin induces transcriptional alterations in its target tissues. However, whether such changes are accompanied by epigenetic changes on the chromatin template encompassing insulin responsive genes is unclear...
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Coupling transcription factor occupancy to nucleosome architecture with DNase-FLASH.
Published: November, 2013

Abstract: It is currently not possible to resolve the genome-wide relationship of transcription factors (TFs) and nucleosomes at the level of individual chromatin templates despite rapidly increasing data on TF and nucleosome occupancy in the human genome. ...
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Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis.
Published: November, 2013

Abstract: The development and severity of inflammatory bowel diseases and other chronic inflammatory conditions can be influenced by host genetic and environmental factors, including signals derived from commensal bacteria. However, the mechanisms that inte...
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Precision-cut liver slices of Atlantic cod (Gadus morhua): An in vitro system for studying the effects of environmental contaminants.
Published: November, 2013

Abstract: The Atlantic cod (Gadus morhua) is an economically important species commonly consumed by humans. The widespread distribution of cod in the North Atlantic Ocean makes it vulnerable to effluents from human activities, such as coastal industries and...
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Promiscuous RNA binding by Polycomb repressive complex 2.
Published: November, 2013

Abstract: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Long noncoding RNAs (lncRNAs) recruit PRC2 to chromatin, but the general role of RNA in maintaining repressed chro...
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MEF2 Is a Converging Hub for Histone Deacetylase 4 and Phosphatidylinositol 3-Kinase/Akt-Induced Transformation.
Published: November, 2013

Abstract: The MEF2-class IIa histone deacetylase (HDAC) axis operates in several differentiation pathways and in numerous adaptive responses. We show here that nuclear active HDAC4 and HDAC7 display transforming capability. HDAC4 oncogenic potential depends...
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Regulation of hypothalamic corticotropin-releasing hormone transcription by elevated glucocorticoids.
Published: November, 2013

Abstract: Negative glucocorticoid feedback is essential for preventing the deleterious effects of excessive hypothalamic pituitary adrenal axis axis activation, with an important target being CRH transcription in the hypothalamic paraventricular nucleus. Th...
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Genomic and proteomic analyses of prdm5 reveal interactions with insulator binding proteins in embryonic stem cells.
Published: November, 2013

Abstract: PRDM proteins belong to the SET domain protein family, which is involved in the regulation of gene expression. Although few PRDM members possess histone methyltransferase activity, the molecular mechanisms by which the other members exert transcri...
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A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue.
Published: November, 2013

Abstract: Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture "authentic" interactions. While ChIP protocols have been optimized for use with spe...
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Expression and regulation of intergenic long noncoding RNAs during T cell development and differentiation.
Published: November, 2013

Abstract: Although intergenic long noncoding RNAs (lincRNAs) have been linked to gene regulation in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here we identified 1,524 lincRNA clusters in 42 T cell samples, from ea...
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Lipopolysaccharide Increases the Incidence of Collagen-Induced Arthritis in Mice Through Induction of Protease HTRA-1 Expression.
Published: November, 2013

Abstract: OBJECTIVE: The protease HTRA-1 is closely associated with rheumatoid arthritis (RA). The molecular mechanisms that control HTRA-1 expression are currently unknown. This study was undertaken to determine the regulatory role of Toll-like receptors (...
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PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
Published: November, 2013

Abstract: EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential for development processes in vivo and for the differentiation of embryonic stem cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive H3K27m...
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Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles.
Published: November, 2013

Abstract: Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole tran...
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The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex.
Published: November, 2013

Abstract: Prostate cancers remain indolent in the majority of individuals but behave aggressively in a minority. The molecular basis for this clinical heterogeneity remains incompletely understood. Here we characterize a long noncoding RNA termed SChLAP1 (s...
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Dynamics of 1α,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes.
Published: November, 2013

Abstract: The signaling cascade of the transcription factor vitamin D receptor (VDR) is triggered by its specific ligand 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study we demonstrate that in THP-1 human monocytic leukemia cells 87.4% of the 1034 mo...
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Mouse BAZ1A (ACF1) is dispensable for double-strand break repair but is essential for averting improper gene expression during spermatogenesis.
Published: November, 2013

Abstract: ATP-dependent chromatin remodelers control DNA access for transcription, recombination, and other processes. Acf1 (also known as BAZ1A in mammals) is a defining subunit of the conserved ISWI-family chromatin remodelers ACF and CHRAC, first purifie...
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The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening.
Published: October, 2013

Abstract: Telomere maintenance by the conventional DNA replication machinery and telomerase is assisted by specialized DNA helicases, nucleases and telomere binding proteins. Here, we identify the THO components at telomeres and define critical roles of thi...
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Ligation bias in illumina next-generation DNA libraries: implications for sequencing ancient genomes.
Published: October, 2013

Abstract: Ancient DNA extracts consist of a mixture of endogenous molecules and contaminant DNA templates, often originating from environmental microbes. These two populations of templates exhibit different chemical characteristics, with the former showing ...
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Fine-Mapping an Association of FSHR with Preterm Birth in a Finnish Population.
Published: October, 2013

Abstract: Preterm birth is a complex disorder defined by gestations of less than 37 weeks. While preterm birth is estimated to have a significant genetic component, relative few genes have been associated with preterm birth. Polymorphism in one such gene, f...
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Diet Alters Both the Structure and Taxonomy of the Ovine Gut Microbial Ecosystem.
Published: October, 2013

Abstract: We surveyed the ruminal metagenomes of 16 sheep under two different diets using Illumina pair-end DNA sequencing of raw microbial DNA extracted from rumen samples. The resulting sequence data were bioinformatically mapped to known prokaryotic 16S ...
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Mu-seq: Sequence-Based Mapping and Identification of Transposon Induced Mutations.
Published: October, 2013

Abstract: Mutations tagged by transposon insertions can be readily mapped and identified in organisms with sequenced genomes. Collections of such mutants allow a systematic analysis of gene function, and can be sequence-indexed to build invaluable resources...
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Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.
Published: October, 2013

Abstract: A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors ...
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A missense mutation accelerating the gating of the lysosomal Cl-/H+-exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle.
Published: October, 2013

Abstract: Chloride/proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either pr...
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A molecular evolution approach to study the roles of tropomyosin in fission yeast.
Published: October, 2013

Abstract: Tropomyosin, a coiled-coil protein that binds along the length of the actin filament, is a universal regulator of the actin cytoskeleton. We have taken a bioinformatics/proteomic approach to studying structure-function relationships in this protei...
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The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification.
Published: October, 2013

Abstract: Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine...
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A functionally conserved Polycomb response element from mouse HoxD complex responds to heterochromatin factors.
Published: October, 2013

Abstract: Anterior-posterior body axis in all bilaterians is determined by the Hox gene clusters that are activated in a spatio-temporal order. This expression pattern of Hox genes is established and maintained by regulatory mechanisms that involve higher o...
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Early adipogenesis is regulated through USP7-mediated deubiquitination of the histone acetyltransferase TIP60.
Published: October, 2013

Abstract: Transcriptional coregulators, including the acetyltransferase Tip60, have a key role in complex cellular processes such as differentiation. Whereas post-translational modifications have emerged as an important mechanism to regulate transcriptional...
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Genome-wide and cell-specific epigenetic analysis challenges the role of polycomb in Drosophila spermatogenesis.
Published: October, 2013

Abstract: The Drosophila spermatogenesis cell differentiation pathway involves the activation of a large set of genes in primary spermatocytes. Most of these genes are activated by testis-specific TATA-binding protein associated factors (tTAFs). In the curr...
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IL-4 blocks TH1-polarizing/inflammatory cytokine gene expression during monocyte-derived dendritic cell differentiation through histone hypoacetylation.
Published: October, 2013

Abstract: BACKGROUND: Whereas recent research has characterized the mechanism by which dendritic cells (DCs) induce TH1/TH17 responses, the functional specialization enabling DCs to polarize TH2 responses remains undefined. Because IL-4 is essential during ...
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Gene dysregulation by histone variant H2A.Z in bladder cancer
Published: October, 2013

Abstract: Background The incorporation of histone variants into nucleosomes is one of the main strategies that the cell uses to regulate the structure and function of chromatin. Histone H2A.Z is an evolutionarily conserved histone H2A variant that is pref...
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The SERRATE protein is involved in alternative splicing in Arabidopsis thaliana.
Published: October, 2013

Abstract: How alternative splicing (AS) is regulated in plants has not yet been elucidated. Previously, we have shown that the nuclear cap-binding protein complex (AtCBC) is involved in AS in Arabidopsis thaliana. Here we show that both subunits of AtCBC (A...
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Gene regulatory scenarios of primary 1,25-dihydroxyvitamin d3 target genes in a human myeloid leukemia cell line.
Published: October, 2013

Abstract: Genome- and transcriptome-wide data has significantly increased the amount of available information about primary 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) target genes in cancer cell models, such as human THP-1 myelomonocytic leukemia cells. In this...
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Evidence of population bottleneck in Astragalus michauxii (Fabaceae), a narrow endemic of the southeastern United States
Published: October, 2013

Abstract: Genetic factors such as decreased genetic diversity and increased homozygosity can have detrimental effects on rare species, and may ultimately limit potential adaptation and exacerbate population declines. The Gulf and Atlantic Coastal Plain phys...
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Blimp1 (Prdm1) prevents re-specification of photoreceptors into retinal bipolar cells by restricting competence.
Published: October, 2013

Abstract: During retinal development, photoreceptors and bipolar cells express the transcription factor Otx2. Blimp1 is transiently expressed in Otx2+ cells. Blimp1 deletion results in excess bipolar cell formation at the expense of photoreceptors. In princ...
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CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation.
Published: October, 2013

Abstract: CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF's binding site sequence may affect the regulation of CTCF recru...
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Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels.
Published: October, 2013

Abstract: The rates of mRNA synthesis and degradation determine cellular mRNA levels and can be monitored by comparative dynamic transcriptome analysis (cDTA) that uses nonperturbing metabolic RNA labeling. Here we present cDTA data for 46 yeast strains lac...
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NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and alters CpG methylation.
Published: October, 2013

Abstract: Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns affectin...
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Sox2 Expression Is Regulated by a Negative Feedback Loop in Embryonic Stem Cells That Involves AKT Signaling and FoxO1.
Published: October, 2013

Abstract: The self-renewal and pluripotency of embryonic stem cells (ESC) is regulated by a highly integrated network of essential transcription factors, which includes Sox2. Previous studies have shown that elevating Sox2 on its own in mouse ESC induces di...
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Combined modulation of polycomb and trithorax genes rejuvenates β cell replication.
Published: October, 2013

Abstract: Inadequate functional β cell mass underlies both type 1 and type 2 diabetes. β Cell growth and regeneration also decrease with age through mechanisms that are not fully understood. Age-dependent loss of enhancer of zeste homolog 2 (EZH2) prevents ...
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Spt6 regulates intragenic and antisense transcription, nucleosome positioning, and histone modifications genome-wide in fission yeast.
Published: October, 2013

Abstract: Spt6 is a highly conserved histone chaperone that interacts directly with both RNA polymerase II and histones to regulate gene expression. To gain a comprehensive understanding of the roles of Spt6, we performed genome-wide analyses of transcripti...
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Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell factor-activated pathways.
Published: October, 2013

Abstract: STEM CELL FACTOR (MOUSE: Kitl, human: KITLG) and insulin-like growth factor-1 (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1...
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A Conserved Protein Motif Is Required for Full Modulatory Activity of Negative Elongation Factor Subunits NELF-A and NELF-B in Modifying Glucocorticoid Receptor-Regulated Gene Induction Properties.
Published: October, 2013

Abstract: NELF-B is a BRCA1-interacting protein and subunit (with NELF-A, -C/D, and -E) of the human negative elongation factor (NELF) complex, which participates in RNA polymerase II pausing shortly after transcription initiation, especially for synchroniz...
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Angiomodulin is required for cardiogenesis of embryonic stem cells and is maintained by a feedback loop network of p63 and Activin-A.
Published: October, 2013

Abstract: The transcription factor p63, member of the p53 gene family, encodes for two main isoforms, TAp63 and ΔNp63 with distinct functions on epithelial homeostasis and cancer. Recently, we discovered that TAp63 is essential for in vitro cardiogenesis an...
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Class I Lysine Deacetylases Facilitate Glucocorticoid-induced Transcription.
Published: October, 2013

Abstract: Nuclear receptors use lysine acetyltransferases and lysine deacetylases (KDACs) in regulating transcription through histone acetylation. Lysine acetyltransferases interact with steroid receptors upon binding of an agonist and are recruited to targ...
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PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome.
Published: October, 2013

Abstract: Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been reported to occur at several repressed genes, but its specific regulation and genomic distribution remained unclear. Here, we show that the type-II protein arginine methyltr...
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Genomic organization of human transcription initiation complexes.
Published: October, 2013

Abstract: The human genome is pervasively transcribed, yet only a small fraction is coding. Here we address whether this non-coding transcription arises at promoters, and detail the interactions of initiation factors TATA box binding protein (TBP), transcri...
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A three-component signaling system finetunes expression kinetics of HPPK responsible for folate synthesis by positive feedback loop during stress response of Xanthomonas campestris.
Published: October, 2013

Abstract: During adaptation to environments, bacteria employ two-component signal transduction systems, which contain histidine kinases and response regulators, to sense and respond to exogenous and cellular stimuli in an accurate spatiotemporal manner. Alt...
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ErbB2 upregulates the Na+,HCO3--cotransporter NBCn1/SLC4A7 in human breast cancer cells via Akt, ERK, Src, and Kruppel-like factor 4.
Published: October, 2013

Abstract: Misregulation of acid-base transport plays central roles in cancer development. We previously demonstrated the strong up-regulation of the Na(+),HCO3(-) cotransporter NBCn1 (SLC4A7) in MCF-7 breast cancer cells by a truncated, constitutively activ...
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Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.
Published: October, 2013

Abstract: The genetic basis of complex neurological disorders involving language are poorly understood, partly due to the multiple additive genetic risk factors that are thought to be responsible. Furthermore, these conditions are often syndromic in that th...
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DNMT1 Is Regulated by ATP-Citrate Lyase and Maintains Methylation Patterns during Adipocyte Differentiation.
Published: October, 2013

Abstract: During adipocyte differentiation, significant epigenomic changes occur in association with the implementation of the adipogenic program. We have previously shown that histone acetylation increases during differentiation in a manner dependent on ac...
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The APSES transcription factor Efg1 is a global regulator that controls morphogenesis and biofilm formation in Candida parapsilosis.
Published: October, 2013

Abstract: Efg1 (a member of the APSES family) is an important regulator of hyphal growth and of the white-to-opaque transition in Candida albicans and very closely related species. We show that in Candida parapsilosis Efg1 is a major regulator of a differen...
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Sumoylation at chromatin governs coordinated repression of a transcriptional program essential for cell growth and proliferation.
Published: October, 2013

Abstract: Despite numerous studies on specific sumoylated transcriptional regulators, the global role of SUMO on chromatin in relation to transcription regulation remains largely unknown. Here, we determined the genome-wide localization of SUMO1 and SUMO2/3...
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Cell-Autonomous Regulation of Brown Fat Identity Gene UCP1 by Unliganded Vitamin D Receptor.
Published: October, 2013

Abstract: White adipose tissue stores energy in the form of lipids, and brown adipose tissue expends energy via uncoupled fatty acid oxidation, which leads to the generation of heat. Obesity reflects an imbalance between energy storage and energy expenditur...
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Dissection of the elements of osmotic stress response transcription factor Hot1 involved in the interaction with MAPK Hog1 and in the activation of transcription.
Published: October, 2013

Abstract: The response to hyperosmotic stress is mediated by the HOG pathway. The MAP kinase Hog1 activates several transcription factors, regulates chromatin-modifying enzymes and, through its interaction with RNA polymerase II, it directs this enzyme to o...
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Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration.
Published: October, 2013

Abstract: Pregnenolone (P5) is a neurosteroid that improves memory and neurological recovery. It is also required for zebrafish embryonic development. However, its mode of action is unclear. Here we show that P5 promotes cell migration and microtubule polym...
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MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma.
Published: October, 2013

Abstract: MEF2B encodes a transcriptional activator and is mutated in ∼11% of diffuse large B cell lymphomas (DLBCLs) and ∼12% of follicular lymphomas (FLs). Here we found that MEF2B directly activated the transcription of the proto-oncogene BCL6 in normal ...
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Oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine.
Published: October, 2013

Abstract: To uncover the function of and interplay between the mammalian cytosine modifications 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), new techniques and advances in current technology are needed. To this end, we have developed oxidative...
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Early histone modifications in the ventromedial hypothalamus and preoptic area following oestradiol administration.
Published: October, 2013

Abstract: Expression of the primary female sex behaviour, lordosis, in laboratory animals depends on oestrogen-induced expression of progesterone receptor (PgR) within a defined cell group in the ventrolateral portion of the ventromedial nucleus of the hypo...
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Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues.
Published: October, 2013

Abstract: Mammalian development requires cytosine methylation, a heritable epigenetic mark of cellular memory believed to maintain a cell's unique gene expression pattern. However, it remains unclear how dynamic DNA methylation relates to cell type-specific...
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Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
Published: October, 2013

Abstract: Viruses that generate capped RNA lacking 2'O methylation on the first ribose are severely affected by the antiviral activity of Type I interferons. We used proteome-wide affinity purification coupled to mass spectrometry to identify human and mous...
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tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans.
Published: October, 2013

Abstract: We describe a new syndrome of young onset diabetes, short stature and microcephaly with intellectual disability in a large consanguineous family with three affected children. Linkage analysis and whole exome sequencing were used to identify the ca...
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Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes.
Published: October, 2013

Abstract: The nuclear lamina is implicated in the organization of the eukaryotic nucleus. Association of nuclear lamins with the genome occurs through large chromatin domains including mostly, but not exclusively, repressed genes. How lamin interactions wit...
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Cap Completion and C-Terminal Repeat Domain Kinase Recruitment Underlie the Initiation-Elongation Transition of RNA Polymerase II.
Published: October, 2013

Abstract: After transcription initiation, RNA polymerase (Pol) II escapes from the promoter and recruits elongation factors. The molecular basis for the initiation-elongation factor exchange during this transition remains poorly understood. Here, we used ch...
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Genome-wide profiling reveals stimulus-specific functions of p53 during differentiation and DNA damage of human embryonic stem cells.
Published: September, 2013

Abstract: How tumor suppressor p53 selectively responds to specific signals, especially in normal cells, is poorly understood. We performed genome-wide profiling of p53 chromatin interactions and target gene expression in human embryonic stem cells (hESCs) ...
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Tissue-specific differences in the regulation of KIBRA gene expression involve transcription factor TCF7L2 and a complex alternative promoter system.
Published: September, 2013

Abstract: KIBRA has been described as a key regulator of the Hippo signaling pathway, regulating organ size control, cell contact inhibition, cell growth, as well as tumorigenesis and cystogenesis. Since there is scarce information on KIBRA gene expression ...
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Gene regulation and priming by topoisomerase IIα in embryonic stem cells.
Published: September, 2013

Abstract: Topoisomerases resolve torsional stress, while their function in gene regulation, especially during cellular differentiation, remains unknown. Here we find that the expression of topo II isoforms, topoisomerase IIα and topoisomerase IIβ, is the ch...
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Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway.
Published: September, 2013

Abstract: The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient's life but is very poorly understood. Here, we...
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Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells.
Published: September, 2013

Abstract: Polycomb repressive complex 2 (PRC2) regulates gene expression during lineage specification through trimethylation of lysine 27 on histone H3 (H3K27me3). In Drosophila, polycomb binding sites are dynamic chromatin regions enriched with the histone...
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Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1.
Published: September, 2013

Abstract: The t(8;21) and inv(16) chromosomal aberrations generate the oncoproteins AML1-ETO (A-E) and CBFβ-SMMHC (C-S). The role of these oncoproteins in acute myeloid leukemia (AML) etiology has been well studied. Conversely, the function of native RUNX1 ...
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Insulin-activated Elk-1 recruits the TIP60/NuA4 complex to increase prolactin gene transcription.
Published: September, 2013

Abstract: Insulin increases prolactin gene expression in GH4 cells through phosphorylation of Elk-1 (Jacob and Stanley, 2001). We preformed a reverse two-hybrid screen using Elk-1-B42 as bait to identify proteins from GH4 cells that might serve as co-activa...
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Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Published: September, 2013

Abstract: The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methyltransferase that cooperates with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESCs), but its function in these...
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Identification of an Enhancer That Increases miR-200b~200a~429 Gene Expression in Breast Cancer Cells.
Published: September, 2013

Abstract: The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for...
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The Reelin receptors ApoER2 and VLDLR are direct target genes of HIC1 (Hypermethylated In Cancer 1).
Published: September, 2013

Abstract: The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) is located in 17p13.3 a region frequently hypermethylated or deleted in tumors and in a contiguous-gene syndrome, the Miller-Dieker syndrome which includes classical lissencephaly (smoot...
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Genome-Wide Analysis of DNA Methylation in Soybean.
Published: September, 2013

Abstract: Cytosine methylation is an important mechanism for dynamical regulation of gene expression. We identified 2162 differentially methylated regions in different soybean organs and further analyzed the interplays among DNA methylation, smRNA abundance...
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The BTB-Containing Protein Kctd15 Is SUMOylated In Vivo.
Published: September, 2013

Abstract: Potassium Channel Tetramerization Domain containing 15 (Kctd15) has a role in regulating the neural crest (NC) domain in the embryo. Kctd15 inhibits NC induction by antagonizing Wnt signaling and by interaction with the transcription factor AP-2α ...
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Verification of Intraovum Transmission of a Microsporidium of Vertebrates: Pseudoloma neurophilia Infecting the Zebrafish, Danio rerio.
Published: September, 2013

Abstract: Direct transmission from parents to offspring, referred to as vertical transmission, occurs within essentially all major groups of pathogens. Several microsporidia (Phylum Microsporidia) that infect arthropods employ this mode of transmission, and...
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An integrated transcriptome and epigenome analysis identifies a novel candidate gene for pancreatic cancer
Published: September, 2013

Abstract: Background Pancreatic cancer is a highly lethal cancer with limited diagnostic and therapeutic modalities. Methods To begin to explore the genomic landscape of pancreatic cancer, we used massively parallel sequencing to catalog and compare tran...
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Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome.
Published: September, 2013

Abstract: Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% of the population inherits a chromosomally integ...
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Geminin Is Required for the Maintenance of Pluripotency
Published: September, 2013

Abstract: Pluripotency requires the expression of the three core transcriptions factors Oct4, Sox2 and Nanog, as well as further, complementary proteins. The geminin protein is part of this network, and was shown to play a role in the regulation of DNA repl...
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Recent Diversification of a Marine Genus (Tursiops spp.) Tracks Habitat Preference and Environmental Change.
Published: September, 2013

Abstract: Understanding the evolution of diversity and the resulting systematics in marine systems is confounded by the lack of clear boundaries in oceanic habitats, especially for highly mobile species like marine mammals. Dolphin populations and sibling s...
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Epigenetic Induction of EGR-1 Expression by the Amyloid Precursor Protein during Exposure to Novelty.
Published: September, 2013

Abstract: Following transcriptome comparison of primary cultures isolated from brain of mice expressing or not the amyloid precursor protein APP, we found transcription of the EGR-1 gene to be regulated by APP. In primary cultures of cortical neurons, APP s...
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MiR-210 Is Induced by Oct-2, Regulates B Cells, and Inhibits Autoantibody Production.
Published: September, 2013

Abstract: MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in t...
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Multivalent Engagement of TFIID to Nucleosomes.
Published: September, 2013

Abstract: The process of eukaryotic transcription initiation involves the assembly of basal transcription factor complexes on the gene promoter. The recruitment of TFIID is an early and important step in this process. Gene promoters contain distinct DNA seq...
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Target Capture and Massively Parallel Sequencing of Ultraconserved Elements (UCEs) for Comparative Studies at Shallow Evolutionary Time Scales
Published: September, 2013

Abstract: Comparative genetic studies of non-model organisms are transforming rapidly due to major advances in sequencing technology. A limiting factor in these studies has been the identification and screening of orthologous loci across an evolutionarily d...
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Direct activation of a mouse Hoxd11 axial expression enhancer by Gdf11/Smad signalling.
Published: September, 2013

Abstract: A Hoxd11/lacZ reporter, expressed with a Hoxd11-like axial expression pattern in transgenic mouse embryos, is stimulated in tailbud fragments when cultured in presence of Gdf11, a TGF-β growth/differentiation factor. The same construct is also sti...
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Proteomics identifies ubiquitin-proteasome targets and new roles for chromatin-remodeling in the Arabidopsis response to phosphate starvation.
Published: September, 2013

Abstract: In order to identify new regulators of the phosphate (Pi) starvation signaling pathway in plants, we analyzed variation in the abundance of nuclear-enriched proteins isolated from Arabidopsis roots that depends on Pi supply. We used 2-D fluorescen...
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Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia.
Published: September, 2013

Abstract: The t(8;21) and inv(16)/t(16;16) rearrangements affecting the core-binding factors RUNX1 and CBFB, respectively, are found in 15% to 20% of adult de novo acute myeloid leukemia (AML) cases and are associated with a favorable prognosis. Since the e...
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Insights into the Loblolly Pine Genome: Characterization of BAC and Fosmid Sequences.
Published: September, 2013

Abstract: Despite their prevalence and importance, the genome sequences of loblolly pine, Norway spruce, and white spruce, three ecologically and economically important conifer species, are just becoming available to the research community. Following the co...
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Evidence from mouse and man for a role of neuregulin 3 in nicotine dependence.
Published: September, 2013

Abstract: Addiction to nicotine and the ability to quit smoking are influenced by genetic factors. We used functional genomic approaches (chromatin immunoprecipitation (ChIP) and whole-genome sequencing) to identify cAMP response element-binding protein (CR...
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The p130 Isoform of Angiomotin Is Required for Yap-Mediated Hepatic Epithelial Cell Proliferation and Tumorigenesis
Published: September, 2013

Abstract: The Hippo-Yap signaling pathway regulates a number of developmental and adult cellular processes, including cell fate determination, tissue growth, and tumorigenesis. Members of the scaffold protein angiomotin (Amot) family interact with several H...
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Global alterations of DNA methylation in cholangiocarcinoma targets the Wnt signaling pathway
Published: September, 2013

Abstract: The molecular mechanisms underlying the genesis of cholangiocarcinomas (CCs) are poorly understood. Epigenetic changes such as aberrant hypermethylation and subsequent atypical gene expression are characteristic features of most human cancers. In ...
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Antisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formation.
Published: September, 2013

Abstract: DNA Topoisomerase I (Top1) is required to relax DNA supercoils generated by RNA polymerases (RNAPs). Top1 is inhibited with high specificity by camptothecin (CPT), an effective anticancer agent, and by oxidative base damage and ribonucleotides in ...
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Phosphorylation of RNA polymerase II is independent of P-TEFb in the C. elegans germline.
Published: September, 2013

Abstract: RNA polymerase II (Pol II) elongation in metazoans is thought to require phosphorylation of serine 2 (Ser2-P) of the Pol II C-terminal domain (CTD) by the P-TEFb complex, CDK-9/cyclin T. Another Ser2 kinase complex, CDK-12/cyclin K, which requires...
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A new strategy for gene targeting and functional proteomics using the DT40 cell line.
Published: September, 2013

Abstract: DT40 cells derived from chicken B lymphocytes exhibit exceptionally high homologous recombination rates. Therefore, they can be used as a convenient tool and model for gene targeting experiments. However, lack of efficient cloning strategies, prot...
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Integrated virus-host methylome analysis in head and neck squamous cell carcinoma
Published: September, 2013

Abstract: One in six cancers worldwide is caused by infection and human papillomavirus (HPV) is one of the main culprits. To better understand the dynamics of HPV integration and its effect on both the viral and host methylomes, we conducted whole-genome DN...
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Chromatin-specific regulation of mammalian rDNA transcription by clustered TTF-I binding sites.
Published: September, 2013

Abstract: Enhancers and promoters often contain multiple binding sites for the same transcription factor, suggesting that homotypic clustering of binding sites may serve a role in transcription regulation. Here we show that clustering of binding sites for t...
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Ago1 Interacts with RNA Polymerase II and Binds to the Promoters of Actively Transcribed Genes in Human Cancer Cells.
Published: September, 2013

Abstract: Argonaute proteins are often credited for their cytoplasmic activities in which they function as central mediators of the RNAi platform and microRNA (miRNA)-mediated processes. They also facilitate heterochromatin formation and establishment of re...
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Unisexual and heterosexual meiotic reproduction generate aneuploidy and phenotypic diversity de novo in the yeast Cryptococcus neoformans.
Published: September, 2013

Abstract: Aneuploidy is known to be deleterious and underlies several common human diseases, including cancer and genetic disorders such as trisomy 21 in Down's syndrome. In contrast, aneuploidy can also be advantageous and in fungi confers antifungal drug ...
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miR-1/133a clusters cooperatively specify the cardiomyogenic lineage by adjustment of myocardin levels during embryonic heart development.
Published: September, 2013

Abstract: miRNAs are small RNAs directing many developmental processes by posttranscriptional regulation of protein-coding genes. We uncovered a new role for miR-1-1/133a-2 and miR-1-2/133a-1 clusters in the specification of embryonic cardiomyocytes allowin...
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A metagenomic snapshot of taxonomic and functional diversity in an alpine glacier cryoconite ecosystem
Published: September, 2013

Abstract: Cryoconite is a microbe–mineral aggregate which darkens the ice surface of glaciers. Microbial process and marker gene PCR-dependent measurements reveal active and diverse cryoconite microbial communities on polar glaciers. Here, we provide the fi...
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Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis resistance in leukaemia.
Published: September, 2013

Abstract: Deregulation of transcriptional networks contributes to haematopoietic malignancies. The transcription factor Spi-1/PU.1 is a master regulator of haematopoiesis and its alteration leads to leukaemia. Spi-1 overexpression inhibits differentiation a...
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Mass production of SNP markers in a nonmodel passerine bird through RAD sequencing and contig mapping to the zebra finch genome.
Published: September, 2013

Abstract: Here, we present an adaptation of restriction-site-associated DNA sequencing (RAD-seq) to the Illumina HiSeq2000 technology that we used to produce SNP markers in very large quantities at low cost per unit in the Réunion grey white-eye (Zosterops ...
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Let-7b and miR-495 Stimulate Differentiation and Prevent Metaplasia of Pancreatic Acinar Cells by Repressing HNF6.
Published: September, 2013

Abstract: BACKGROUND & AIMS: Diseases of the exocrine pancreas are often associated with perturbed differentiation of acinar cells. MicroRNAs (miRNAs) regulate pancreas development, yet little is known about their contribution to acinar cell differentiation...
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The ASAP2 gene is a primary target of 1,25-dihydroxyvitamin D3 in human monocytes and macrophages.
Published: August, 2013

Abstract: A genome-wide data set on vitamin D receptor (VDR) binding sites in human THP-1 cells (monocytes) led us to the genomic region around the ASAP2 (Arf-GAP with SH3 domain, ankyrin repeat and PH domain 2) gene, whose product is involved in the regula...
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Long range epigenetic silencing is a trans-species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells.
Published: August, 2013

Abstract: DNA methylation and chromatin remodeling are frequently implicated in the silencing of genes involved in carcinogenesis. Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and ha...
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Endogenous Nuclear RNAi Mediates Behavioral Adaptation to Odor.
Published: August, 2013

Abstract: Most eukaryotic cells express small regulatory RNAs. The purpose of one class, the somatic endogenous siRNAs (endo-siRNAs), remains unclear. Here, we show that the endo-siRNA pathway promotes odor adaptation in C. elegans AWC olfactory neurons. In...
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Transcriptional environment and chromatin architecture interplay dictates globin expression patterns of heterospecific hybrids derived from undifferentiated human embryonic stem cells or from their erythroid progeny.
Published: August, 2013

Abstract: To explore the response of β globin locus with established chromatin domains upon their exposure to new transcriptional environments, we transferred the chromatin-packaged β globin locus of undifferentiated human embryonic stem cells (hESCs) or hE...
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PRC2 Controls Drosophila Oocyte Cell Fate by Repressing Cell Cycle Genes.
Published: August, 2013

Abstract: The oocyte is a unique cell type that undergoes extensive chromosome changes on its way to fertilization, but the chromatin determinants of its fate are unknown. Here, we show that Polycomb group (PcG) proteins of the Polycomb repressive complex 2...
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A signature motif mediating selective interactions of BCL11A with the NR2E/F subfamily of orphan nuclear receptors.
Published: August, 2013

Abstract: Despite their physiological importance, selective interactions between nuclear receptors (NRs) and their cofactors are poorly understood. Here, we describe a novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that facilitat...
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Enhanced Chromatin Dynamics by FACT Promotes Transcriptional Restart after UV-Induced DNA Damage.
Published: August, 2013

Abstract: Chromatin remodeling is tightly linked to all DNA-transacting activities. To study chromatin remodeling during DNA repair, we established quantitative fluorescence imaging methods to measure the exchange of histones in chromatin in living cells. W...
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Optical control of mammalian endogenous transcription and epigenetic states.
Published: August, 2013

Abstract: The dynamic nature of gene expression enables cellular programming, homeostasis and environmental adaptation in living systems. Dissection of causal gene functions in cellular and organismal processes therefore necessitates approaches that enable ...
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A GAA repeat expansion reporter model of Friedreich's ataxia recapitulates the genomic context and allows rapid screening of therapeutic compounds.
Published: August, 2013

Abstract: Friedreich's ataxia (FRDA) is caused by large GAA expansions in intron 1 of the frataxin gene (FXN), which lead to reduced FXN expression through a mechanism not fully understood. Understanding such mechanism is essential for the identification of...
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Conserved Regulators of Nucleolar Size Revealed by Global Phenotypic Analyses
Published: August, 2013

Abstract: Regulation of cell growth is a fundamental process in development and disease that integrates a vast array of extra- and intracellular information. A central player in this process is RNA polymerase I (Pol I), which transcribes ribosomal RNA (rRNA...
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Sexually Dimorphic Genome-Wide Binding of Retinoid X Receptor alpha (RXRα) Determines Male-Female Differences in the Expression of Hepatic Lipid Processing Genes in Mice.
Published: August, 2013

Abstract: Many hepatic functions including lipid metabolism, drug metabolism, and inflammatory responses are regulated in a sex-specific manner due to distinct patterns of hepatic gene expression between males and females. Regulation for the majority of the...
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PARP-1 Controls Immunosuppressive Function of Regulatory T Cells by Destabilizing Foxp3.
Published: August, 2013

Abstract: Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme and transcription factor that is involved in inflammatory response, but its role in T cell response remains largely unknown. We show here that PARP-1 regulates the suppressive function of...
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Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML.
Published: August, 2013

Abstract: Mutations in the metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are frequently found in glioma, acute myeloid leukemia (AML), melanoma, thyroid cancer and chondrosarcoma patients. Mutant IDH produces 2-hydroxyglutarate (2HG), whi...
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Systematic Identification of Proteins Binding to Chromatin-Embedded Ubiquitylated H2B Reveals Recruitment of SWI/SNF to Regulate Transcription.
Published: August, 2013

Abstract: Chromatin posttranslational modifications (PTMs), including monoubiquitylation of histone H2B on lysine 120 (H2Bub1), play a major role in regulating genome functions. To elucidate the molecular mechanisms of H2Bub1 activity, a chromatin template ...
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CDK8-Mediated STAT1-S727 Phosphorylation Restrains NK Cell Cytotoxicity and Tumor Surveillance.
Published: August, 2013

Abstract: The transcription factor STAT1 is important in natural killer (NK) cells, which provide immediate defense against tumor and virally infected cells. We show that mutation of a single phosphorylation site (Stat1-S727A) enhances NK cell cytotoxicity ...
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WT1 regulates the expression of inhibitory chemokines during heart development.
Published: August, 2013

Abstract: The embryonic epicardium is an important source of cardiovascular precursor cells and paracrine factors that are required for adequate heart formation. Signaling pathways regulated by WT1 that promote heart development have started to be described...
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Mod5 protein binds to tRNA gene complexes and affects local transcriptional silencing.
Published: August, 2013

Abstract: The tRNA gene-mediated (tgm) silencing of RNA polymerase II promoters is dependent on subnuclear clustering of the tRNA genes, but genetic analysis shows that the silencing requires additional mechanisms. We have identified proteins that bind tRNA...
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Artd1/Parp1 regulates reprogramming by transcriptional regulation of Fgf4 via Sox2 ADP-ribosylation.
Published: August, 2013

Abstract: The recently established reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by Takahashi and Yamanaka, represents a valuable tool for future therapeutic applications. To date, the mechanisms underlying this process are stil...
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A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.
Published: August, 2013

Abstract: In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the ...
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Chromatin-Bound IκBα Regulates a Subset of Polycomb Target Genes in Differentiation and Cancer.
Published: August, 2013

Abstract: IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chroma...
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A three-state model for the regulation of telomerase by TERRA and hnRNPA1.
Published: August, 2013

Abstract: Telomeres, the physical ends of eukaryotic chromosomes, are transcribed into telomeric repeat-containing RNA (TERRA), a large non-coding RNA, which forms an integral part of telomeric heterochromatin. In vitro, naked TERRA molecules are efficient ...
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Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons.
Published: August, 2013

Abstract: Polycomb Repressive Complex 2 (PRC2) mediates transcriptional silencing by catalyzing histone H3 lysine 27 trimethylation (H3K27me3), but its role in the maturation of postmitotic mammalian neurons remains largely unknown. We report that the PRC2 ...
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Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
Published: August, 2013

Abstract: DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germ line, and may be mediated by Tet (ten eleven t...
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Histone variant Htz1 promotes histone H3 acetylation to enhance nucleotide excision repair in Htz1 nucleosomes.
Published: August, 2013

Abstract: Nucleotide excision repair (NER) is critical for maintaining genome integrity. How chromatin dynamics are regulated to facilitate this process in chromatin is still under exploration. We show here that a histone H2A variant, Htz1 (H2A.Z), in nucle...
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Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.
Published: August, 2013

Abstract: BACKGROND: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body...
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Model selection reveals control of cold signalling by evening-phased components of the plant circadian clock.
Published: August, 2013

Abstract: Circadian clocks confer advantages by restricting biological processes to certain times of day through the control of specific phased outputs. Control of temperature signalling is an important function of the plant oscillator, but the architecture...
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Mitochondrial genome linearization is a causative factor for cardiomyopathy in mice and Drosophila.
Published: August, 2013

Abstract: Aims: Mitofusin (Mfn) 2 redundantly promotes mitochondrial outer membrane tethering and organelle fusion with Mfn1, and uniquely functions as the mitochondrial receptor for Parkin during PINK1-Parkin mediated mitophagy. Selective deletion of Mfn2 ...
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A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection.
Published: August, 2013

Abstract: Pathogens dramatically affect host cell transcription programs for their own profit during infection, but in most cases, the underlying mechanisms remain elusive. We found that during infection with the bacterium Listeria monocytogenes, the host d...
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O-glycosylation as a novel control mechanism of peptidoglycan hydrolase activity.
Published: August, 2013

Abstract: Acm2, the major autolysin of Lactobacillus plantarum, is a tripartite protein. Its catalytic domain is surrounded by an O-glycosylated N-terminal region rich in Ala, Ser, and Thr (AST domain), which is of low complexity and unknown function, and a...
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Genome-wide profiling identifies a subset of methamphetamine (METH)-induced genes associated with METH-induced increased H4K5Ac binding in the rat striatum.
Published: August, 2013

Abstract: BACKGROUND: METH is an illicit drug of abuse that influences gene expression in the rat striatum. Histone modifications regulate gene transcription. METHODS: We therefore used microarray analysis and genome-scale approaches to examine potential re...
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Binding of TFIIIC to SINE Elements Controls the Relocation of Activity-Dependent Neuronal Genes to Transcription Factories.
Published: August, 2013

Abstract: In neurons, the timely and accurate expression of genes in response to synaptic activity relies on the interplay between epigenetic modifications of histones, recruitment of regulatory proteins to chromatin and changes to nuclear structure. To ide...
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H2A.Z Acidic Patch Couples Chromatin Dynamics to Regulation of Gene Expression Programs during ESC Differentiation.
Published: August, 2013

Abstract: The histone H2A variant H2A.Z is essential for embryonic development and for proper control of developmental gene expression programs in embryonic stem cells (ESCs). Divergent regions of amino acid sequence of H2A.Z likely determine its functional...
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Ras-Induced Changes in H3K27me3 Occur after Those in Transcriptional Activity.
Published: August, 2013

Abstract: Oncogenic signaling pathways regulate gene expression in part through epigenetic modification of chromatin including DNA methylation and histone modification. Trimethylation of histone H3 at lysine-27 (H3K27), which correlates with transcriptional...
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Androgen Receptor Drives Transcription of Rat PACAP in Gonadotrope Cells.
Published: August, 2013

Abstract: Gonadotropin expression is precisely regulated within the hypothalamic-pituitary-gonadal axis through the complex interaction of neuropeptides, gonadal steroids. and both gonadal- and pituitary-derived peptides. In the anterior pituitary gland, th...
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High-throughput sequencing reveals principles of adeno-associated virus serotype 2 integration.
Published: August, 2013

Abstract: Viral integrations are important in human biology, yet genome-wide integration profiles have not been determined for many viruses. Adeno-associated virus (AAV) infects most of the human population and is a prevalent gene therapy vector. AAV integr...
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Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells.
Published: August, 2013

Abstract: The effects of diverse stresses on promoter selectivity and transcription regulation by the tumor suppressor p53 are poorly understood. We have taken a comprehensive approach to characterizing the human p53 network that includes p53 levels, bindin...
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Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility.
Published: August, 2013

Abstract: The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental questio...
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Minotaur is critical for primary piRNA biogenesis.
Published: August, 2013

Abstract: Piwi proteins and their associated small RNAs are essential for fertility in animals. In part, this is due to their roles in guarding germ cell genomes against the activity of mobile genetic elements. piRNA populations direct Piwi proteins to sile...
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Early growth response 2 (Egr2) plays opposing roles in committing C3H10T1/2 stem cells to adipocytes and smooth muscle-like cells.
Published: August, 2013

Abstract: Early growth response 2 (Egr2) is a zinc-finger transcription factor that acts as an important modulator of a variety of physiological processes, such as cell differentiation, proliferation and apoptosis. Here we showed that Egr2 was downregulated...
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Chromatin tandem affinity purification sequencing.
Published: August, 2013

Abstract: Chromatin immunoprecipitation coupled with ultra-high-throughput sequencing (ChIP-seq) is a widely used method for mapping the interactions of proteins with DNA. However, the requirements for ChIP-grade antibodies impede wider application of this ...
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Chromatin-modifying agents reactivate embryonic renal stem/progenitor genes in human adult kidney epithelial cells but abrogate dedifferentiation and stemness.
Published: August, 2013

Abstract: Abstract Recent studies have suggested that epigenetic modulation with chromatin-modifying agents can induce stemness and dedifferentiation and increase developmental plasticity. For instance, valproic acid (VPA), a histone deacetylase (HDAC) inhi...
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Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy.
Published: August, 2013

Abstract: The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and the inflammatory response in macrophages. We show here that Rev-erb-α is highly expressed in oxidative skeletal muscle and that its deficiency in muscl...
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BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint.
Published: August, 2013

Abstract: The B cell-specific transcription factor BACH2 is required for affinity maturation of B cells. Here we show that Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglob...
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Noncoding RNAs prevent spreading of a repressive histone mark.
Published: August, 2013

Abstract: Transcription of eukaryotic genomes is more widespread than was previously anticipated and results in the production of many non-protein-coding RNAs (ncRNAs) whose functional relevance is poorly understood. Here we demonstrate that ncRNAs can coun...
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Prdm1a directly activates foxd3 and tfap2a during zebrafish neural crest specification.
Published: August, 2013

Abstract: The neural crest comprises multipotent precursor cells that are induced at the neural plate border by a series of complex signaling and genetic interactions. Several transcription factors, termed neural crest specifiers, are necessary for early ne...
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Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans.
Published: July, 2013

Abstract: The red blood cell related traits are highly heritable but their genetics are poorly defined. Only 5-10% of the total observed variance is explained by the genetic loci found to date, suggesting that additional loci should be searched using approa...
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Silencing MED1 sensitizes breast cancer cells to pure anti-estrogen fulvestrant in vitro and in vivo.
Published: July, 2013

Abstract: Pure anti-estrogen fulvestrant has been shown to be a promising ER antagonist for locally advanced and metastatic breast cancer. Unfortunately, a significant proportion of patients developed resistance to this type of endocrine therapy but the mol...
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Zfp819, a novel KRAB-zinc finger protein, interacts with KAP1 and functions in genomic integrity maintenance of mouse embryonic stem cells.
Published: July, 2013

Abstract: Pluripotency is maintained by both known and unknown transcriptional regulatory networks. In the present study, we have identified Zfp819, a KRAB-zinc finger protein, as a novel pluripotency-related factor and characterized its role in pluripotent...
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Synchronous recruitment of epigenetic modifiers to endotoxin synergistically activated Tnf-α gene in acute kidney injury.
Published: July, 2013

Abstract: BACKGROUND: As a consequence of acute kidney injury (AKI), proximal tubular cells hyperrespond to endotoxin (lipopolysaccharide, LPS) by exaggerated renal Tnf-α Production. This LPS hyperresponsiveness is transcriptionally mediated. The epigenetic...
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STAT3 signaling induces the differentiation of human ICOS(+) CD4 T cells helping B lymphocytes.
Published: July, 2013

Abstract: The generation of high-affinity antibodies and the development of B cell memory are dependent on the help provided by CD4 T cells. Mouse studies indicate that STAT3 signaling in CD4 T cells promotes the acquisition of the B cell help function. How...
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DNA unmethylome profiling by covalent capture of CpG sites.
Published: July, 2013

Abstract: Dynamic patterns of cytosine-5 methylation and successive hydroxylation are part of epigenetic regulation in eukaryotes, including humans, which contributes to normal phenotypic variation and disease risk. Here we present an approach for the mappi...
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Chromatin insulator bodies are nuclear structures that form in response to osmotic stress and cell death.
Published: July, 2013

Abstract: Chromatin insulators assist in the formation of higher-order chromatin structures by mediating long-range contacts between distant genomic sites. It has been suggested that insulators accomplish this task by forming dense nuclear foci termed insul...
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DNA methylation of dermal MSCs in psoriasis: Identification of epigenetically dysregulated genes.
Published: July, 2013

Abstract: BACKGROUND: Mesenchymal stem cells (MSCs) are likely involved in pathological processes of immune-related diseases, including psoriasis, because of their immunoregulatory and pro-angiogenic effects. DNA methylation plays an essential role in regul...
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An epigenetic trap stabilizes singular olfactory receptor expression.
Published: July, 2013

Abstract: The molecular mechanisms regulating olfactory receptor (OR) expression in the mammalian nose are not yet understood. Here, we identify the transient expression of histone demethylase LSD1 and the OR-dependent expression of adenylyl cyclase 3 (Adcy...
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Transcriptional profiling by RNA-Seq of peri-attachment porcine embryos generated by a variety of assisted reproductive technologies.
Published: July, 2013

Abstract: Substantial mortality of in vitro manipulated porcine embryos is observed during peri-attachment development. Herein we describe our efforts to characterize the transcriptomes of embryonic disc (ED) and trophectoderm (TE) cells from porcine embryo...
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PfSec13 is an unusual chromatin-associated nucleoporin of Plasmodium falciparum that is essential for parasite proliferation in human erythrocytes.
Published: July, 2013

Abstract: In Plasmodium falciparum, the deadliest form of human malaria, the nuclear periphery has drawn much attention due to its role as a sub-nuclear compartment involved in virulence gene expression. Recent data have implicated components of the nuclear...
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STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation.
Published: July, 2013

Abstract: CD4(+) T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ. IL-4-producing Th2 effector cells give rise to a long-lived memory ...
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Otx2 and onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors.
Published: July, 2013

Abstract: Cone photoreceptors carry out phototransduction in daylight conditions and provide the critical first step in color vision. Despite their importance, little is known about the developmental mechanisms involved in their generation, particularly how...
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Subnuclear partitioning of rRNA genes between the nucleolus and nucleoplasm reflects alternative epiallelic states.
Published: July, 2013

Abstract: Eukaryotes can have thousands of 45S ribosomal RNA (rRNA) genes, many of which are silenced during development. Using fluorescence-activated sorting techniques, we show that active rRNA genes in Arabidopsis thaliana are present within sorted nucle...
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Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction.
Published: July, 2013

Abstract: Since their discovery, cell-penetrating peptides (CPPs) have provided a novel, efficient, and non-invasive mode of transport for various (bioactive) cargos into cells. Despite the ever-growing number of successful implications of the CPP-mediated ...
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Hmgb1 can facilitate activation of the matrilin-1 gene promoter by Sox9 and L-Sox5/Sox6 in early steps of chondrogenesis.
Published: July, 2013

Abstract: The architectural high mobility group box 1 (Hmgb1) protein acts as both a nuclear and an extracellular regulator of various biological processes, including skeletogenesis. Here we report its contribution to the evolutionarily conserved, distincti...
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De Novo Mutations in the Genome Organizer CTCF Cause Intellectual Disability.
Published: July, 2013

Abstract: An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screen...
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De Novo DNA Methylation in the Male Germ Line Occurs by Default but Is Excluded at Sites of H3K4 Methylation.
Published: July, 2013

Abstract: To understand what dictates the emerging patterns of de novo DNA methylation in the male germline, we mapped DNA methylation, chromatin, and transcription changes in purified fetal mouse germ cells by using methylated CpG island recovery assay (MI...
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PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum
Published: July, 2013

Abstract: The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which is expressed on the surface of P. falciparum-infected red blood cells, is a critical virulence factor for malaria1. Each parasite has 60 antigenically distinc...
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A robust dry reagent lateral flow assay for diagnosis of active schistosomiasis by detection of Schistosoma circulating anodic antigen.
Published: July, 2013

Abstract: An earlier reported laboratory assay, performed in The Netherlands, to diagnose Schistosoma infections by detection of the parasite antigen CAA in serum was converted to a more user-friendly format with dry reagents. The improved assay requires le...
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Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer.
Published: July, 2013

Abstract: The androgen receptor (AR) and the phosphoinositide 3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin (mTOR) signaling are two of the major proliferative pathways in a number of tissues and are the main therapeutic targets in various ...
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Beyond the binding site: in vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development.
Published: July, 2013

Abstract: CNBP is a nucleic acid chaperone implicated in vertebrate craniofacial development, as well as in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human muscle diseases. CNBP is highly conserved among vertebrates and has...
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Digital genotyping of sorghum -- a diverse plant species with a large repeat-rich genome.
Published: July, 2013

Abstract: BACKGROUND: Rapid acquisition of accurate genotyping information is essential for all genetic marker-based studies. For species with relatively small genomes, complete genome resequencing is a feasible approach for genotyping; however, for species...
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PP1α, PP1β and Wip-1 regulate H4S47 phosphorylation and deposition of histone H3 variant H3.3.
Published: July, 2013

Abstract: Phosphorylation of histone H4 serine 47 (H4S47ph) is catalyzed by Pak2, a member of the p21-activated serine/threonine protein kinase (Pak) family and regulates the deposition of histone variant H3.3. However, the phosphatase(s) involved in the re...
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Modifications of Chromatin Dynamics Control the Smad2 Pathway Activation in Aneurysmal Smooth Muscle Cells.
Published: July, 2013

Abstract: Rationale: The activation of the Smad2 signaling pathway is thought to play an important role in human aneurysmal diseases as described by an important body of research. We previously showed that constitutive Smad2 activation is associated with Sm...
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Detection of histone modification by chromatin immunoprecipitation combined zinc finger luciferase-based bioluminescence resonance energy transfer assay.
Published: July, 2013

Abstract: Epigenetic modification such as DNA methylation and histone modification have important roles in gene regulation. Epigenetic modification can be altered by environmental influences and are related to diseases. Therefore, epigenetic modifications m...
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Submergence Confers Immunity Mediated by the WRKY22 Transcription Factor in Arabidopsis.
Published: July, 2013

Abstract: Transcriptional control plays an important role in regulating submergence responses in plants. Although numerous genes are highly induced during hypoxia, their individual roles in hypoxic responses are still poorly understood. Here, we found that ...
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Epigenetic induction of the Ink4a/Arf locus prevents Schwann cell overproliferation during nerve regeneration and after tumorigenic challenge.
Published: July, 2013

Abstract: The number of Schwann cells is fitted to axonal length in peripheral nerves. This relationship is lost when tumorigenic stimuli induce uncontrolled Schwann cell proliferation, generating tumours such us neurofibromas and schwannomas. Schwann cells...
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Changes in RNA polymerase II progression influence somatic hypermutation of Ig-related genes by AID.
Published: July, 2013

Abstract: Somatic hypermutation (SHM) of Ig genes is initiated by the activation-induced cytidine deaminase (AID), and requires target gene transcription. We previously proposed that AID may associate with the RNA polymerase II (Pol). Here, to determine asp...
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Uniform, optimal signal processing of mapped deep-sequencing data.
Published: July, 2013

Abstract: Despite their apparent diversity, many problems in the analysis of high-throughput sequencing data are merely special cases of two general problems, signal detection and signal estimation. Here we adapt formally optimal solutions from signal proce...
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Genome-wide measurement of protein-DNA binding dynamics using competition ChIP.
Published: July, 2013

Abstract: Competition chromatin immunoprecipitation (competition ChIP) enables experimenters to measure protein-DNA dynamics at a single locus or across the entire genome, depending on the detection method. Competition ChIP relies on a cell containing two c...
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Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia.
Published: July, 2013

Abstract: Severe aplastic anemia (AA) is a bone marrow (BM) failure (BMF) disease frequently caused by aberrant immune destruction of blood progenitors. Although a Th1-mediated pathology is well described for AA, molecular mechanisms driving disease progres...
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Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1γ in reprogramming to pluripotency.
Published: July, 2013

Abstract: Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) involves a marked reorganization of chromatin. To identify post-translational histone modifications that change in global abundance during this process, we have applied a q...
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The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals.
Published: July, 2013

Abstract: Glucocorticoid receptor (GR) binds to genomic response elements and regulates gene transcription with cell and gene specificity. Within a response element, the precise sequence to which the receptor binds has been implicated in directing its struc...
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Alu Elements in ANRIL Non-Coding RNA at Chromosome 9p21 Modulate Atherogenic Cell Functions through Trans-Regulation of Gene Networks.
Published: July, 2013

Abstract: The chromosome 9p21 (Chr9p21) locus of coronary artery disease has been identified in the first surge of genome-wide association and is the strongest genetic factor of atherosclerosis known today. Chr9p21 encodes the long non-coding RNA (ncRNA) an...
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Disease-Related Growth Factor and Embryonic Signaling Pathways Modulate an Enhancer of TCF21 Expression at the 6q23.2 Coronary Heart Disease Locus.
Published: July, 2013

Abstract: Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and...
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Stepwise activation of the ATR signaling pathway upon increasing replication stress impacts fragile site integrity.
Published: July, 2013

Abstract: Breaks at common fragile sites (CFS) are a recognized source of genome instability in pre-neoplastic lesions, but how such checkpoint-proficient cells escape surveillance and continue cycling is unknown. Here we show, in lymphocytes and fibroblast...
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Stalled RNAP-II molecules bound to non-coding rDNA spacers are required for normal nucleolus architecture.
Published: July, 2013

Abstract: The correct distribution of nuclear domains is critical for the maintenance of normal cellular processes such as transcription and replication, which are regulated depending on their location and surroundings. The most well-characterized nuclear d...
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A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen.
Published: July, 2013

Abstract: Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in...
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Zeb1 Regulates E-cadherin and Epcam (Epithelial Cell Adhesion Molecule) Expression to Control Cell Behavior in Early Zebrafish Development.
Published: June, 2013

Abstract: The ZEB1 transcription factor is best known as an inducer of epithelial-mesenchymal transitions (EMT) in cancer metastasis, acting through transcriptional repression of CDH1 (encoding E-cadherin) and the EMT-suppressing microRNA-200s (miR-200s). H...
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The genomic landscape of the somatic linker histone subtypes h1.1 to h1.5 in human cells.
Published: June, 2013

Abstract: Human cells contain five canonical, replication-dependent somatic histone H1 subtypes (H1.1, H1.2, H1.3, H1.4, and H1.5). Although they are key chromatin components, the genomic distribution of the H1 subtypes is still unknown, and their role in c...
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Status epilepticus triggers early and late alterations in brain-derived neurotrophic factor and NMDA glutamate receptor Grin2b DNA methylation levels in the hippocampus.
Published: June, 2013

Abstract: Status epilepticus (SE) triggers abnormal expression of genes in the hippocampus, such as glutamate receptor subunit epsilon-2 (Grin2b/Nr2b) and brain-derived neurotrophic factor (Bdnf), that is thought to occur in temporal lobe epilepsy (TLE). We...
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Bivalent chromatin marks developmental regulatory genes in the mouse embryonic germline in vivo.
Published: June, 2013

Abstract: Developmental regulatory genes have both activating (H3K4me3) and repressive (H3K27me3) histone modifications in embryonic stem cells (ESCs). This bivalent configuration is thought to maintain lineage commitment programs in a poised state. However...
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PLK1 signaling in breast cancer cells cooperates with estrogen receptor-dependent gene transcription.
Published: June, 2013

Abstract: Polo-like kinase 1 (PLK1) is a key regulator of cell division and is overexpressed in many types of human cancers. Compared to its well-characterized role in mitosis, little is known about PLK1 functions in interphase. Here, we report that PLK1 me...
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Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells.
Published: June, 2013

Abstract: T cell-intrinsic transforming growth factor β (TGFβ) receptor signaling plays an essential role in controlling immune responses. The RING-type E3 ligase Cbl-b has been shown to mediate the sensitivity of T cells to TGFβ; however, the mechanism und...
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LOcating non-unique matched tags (LONUT) to improve the detection of the enriched regions for ChIP-seq data.
Published: June, 2013

Abstract: One big limitation of computational tools for analyzing ChIP-seq data is that most of them ignore non-unique tags (NUTs) that match the human genome even though NUTs comprise up to 60% of all raw tags in ChIP-seq data. Effectively utilizing these ...
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The Role of SIRT6 Protein in Aging and Reprogramming of Human Induced Pluripotent Stem Cells.
Published: June, 2013

Abstract: Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of transcription, genome stability, telomere integrity, DNA repair, and metabolic homeostas...
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Epigenetic regulation of microRNA expression in renal cell carcinoma.
Published: June, 2013

Abstract: The underlying mechanisms of microRNA deregulation in cancer cells include epigenetic modifications, which play a crucial role in carcinogenesis. We demonstrate that numerous microRNAs are induced in renal cell carcinoma cell lines after treatment...
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Jpx RNA activates Xist by evicting CTCF.
Published: June, 2013

Abstract: In mammals, dosage compensation between XX and XY individuals occurs through X chromosome inactivation (XCI). The noncoding Xist RNA is expressed and initiates XCI only when more than one X chromosome is present. Current models invoke a dependency...
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Improved genetic testing for monogenic diabetes using targeted next-generation sequencing.
Published: June, 2013

Abstract: AIMS/HYPOTHESIS: Current genetic tests for diagnosing monogenic diabetes rely on selection of the appropriate gene for analysis according to the patient's phenotype. Next-generation sequencing enables the simultaneous analysis of multiple genes in...
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Myc binds the pluripotency factor Utf1 through the basic-helix-loop-helix leucine zipper domain.
Published: June, 2013

Abstract: In order to elucidate the function of Myc in the maintenance of pluripotency and self-renewal in mouse embryonic stem cells (mESCs), we screened for novel ESC-specific interactors of Myc by mass spectrometry. Undifferentiated embryonic cell transc...
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Senescence-associated lncRNAs: senescence-associated long noncoding RNAs.
Published: June, 2013

Abstract: Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functional...
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Distinct Roles for CBP and p300 on the RA-Mediated Expression of the Meiosis Commitment Gene Stra8 in Mouse Embryonic Stem Cells.
Published: June, 2013

Abstract: In mammalian germ cells, meiotic commitment requires the expression of Stimulated by retinoic acid gene 8 (Stra8), which is transcriptionally activated by retinoic acid (RA). However, little is known about the epigenetic mechanism by which RA indu...
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The histone deacetylase inhibitor SAHA acts in synergism with fenretinide and doxorubicin to control growth of rhabdoid tumor cells.
Published: June, 2013

Abstract: BACKGROUND: Rhabdoid tumors are highly aggressive malignancies affecting infants and very young children. In many instances these tumors are resistant to conventional type chemotherapy necessitating alternative approaches. METHODS: Proliferation a...
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Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity.
Published: June, 2013

Abstract: Brain plasticity is often restricted to critical periods in early life. Here, we show that a key regulator of this process in the visual cortex, Otx2 homeoprotein, is synthesized and secreted globally from the choroid plexus. Consequently, Otx2 is...
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Centromere binding and a conserved role in chromosome stability for SUMO-dependent ubiquitin ligases.
Published: June, 2013

Abstract: The Saccharomyces cerevisiae Slx5/8 complex is the founding member of a recently defined class of SUMO-targeted ubiquitin ligases (STUbLs). Slx5/8 has been implicated in genome stability and transcription, but the precise contribution is unclear. ...
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Temporal transcriptional response to ethylene gas drives growth hormone cross-regulation in Arabidopsis
Published: June, 2013

Abstract: The gaseous plant hormone ethylene regulates a multitude of growth and developmental processes. How the numerous growth control pathways are coordinated by the ethylene transcriptional response remains elusive. We characterized the dynamic ethyle...
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Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing.
Published: June, 2013

Abstract: Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder...
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Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells.
Published: June, 2013

Abstract: BACKGROUND: In mouse embryonic stem cells (mESCs), transcriptional silencing of numerous class I and II endogenous retroviruses (ERVs), including IAP, ETn and MMERVK10C, is dependent upon the H3K9 methyltransferase (KMTase) SETDB1/ESET and its bin...
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Autolysosomal β-catenin degradation regulates Wnt-autophagy-p62 crosstalk
Published: June, 2013

Abstract: The Wnt/β-catenin signalling and autophagy pathways each play important roles during development, adult tissue homeostasis and tumorigenesis. Here we identify the Wnt/β-catenin signalling pathway as a negative regulator of both basal and stress-in...
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HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas.
Published: June, 2013

Abstract: High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are high