Smc5/6 silences episomal transcription by a three-step function. Published: September, 2022 Abstract:
In addition to its role in chromosome maintenance, the six-membered Smc5/6 complex functions as a restriction factor that binds to and transcriptionally silences viral and other episomal DNA. However, the underlying mechanism is unknown. Here, we ... Read more »
Hexokinase 2 is a transcriptional target and a positive modulator ofAHR signalling. Published: May, 2022 Abstract:
The aryl hydrocarbon receptor (AHR) regulates the expression of numerous genes in response to activation by agonists including xenobiotics. Although it is well appreciated that environmental signals and cell intrinsic features may modulate this tr... Read more »
Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes Published: May, 2022 Abstract:
Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used... Read more »
Effects of GSK-J4 on JMJD3 Histone Demethylase in MouseProstate Cancer Xenografts. Published: January, 2022 Abstract:
BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has b... Read more »
Comprehensive characterization of the epigenetic landscape in Multiple
Myeloma Published: January, 2022 Abstract:
Background: Human multiple myeloma (MM) cell lines (HMCLs) have
been widely used to understand the molecular processes that drive MM
biology. Epigenetic modifications are involved in MM development,
progression, and drug resistance. A comprehensiv... Read more »
SUV39 SET domains mediate crosstalk of heterochromatic histone marks. Published: September, 2021 Abstract:
The SUV39 class of methyltransferase enzymes deposits histone H3 lysine 9 di- and trimethylation (H3K9me2/3), the hallmark of constitutive heterochromatin. How these enzymes are regulated to mark specific genomic regions as heterochromatic is poor... Read more »
N-Methyladenosine co-transcriptionally directs the demethylation of histoneH3K9me2. Published: August, 2020 Abstract:
A dynamic epigenome is critical for appropriate gene expression in development and health. Central to this is the intricate process of transcription, which integrates cellular signaling with chromatin changes, transcriptional machinery and modific... Read more »
Methylation in pericytes after acute injury promotes chronic kidneydisease. Published: August, 2020 Abstract:
The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injur... Read more »
Targeted bisulfite sequencing for biomarker discovery. Published: August, 2020 Abstract:
Cytosine methylation is one of the best studied epigenetic modifications. In mammals, DNA methylation patterns vary among cells and is mainly found in the CpG context. DNA methylation is involved in important processes during development and diffe... Read more »
Proteomics Links Ubiquitin Chain Topology Change to Transcription Factor Activation. Published: August, 2019 Abstract:
A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quan... Read more »
p73 regulates epidermal wound healing and induced keratinocyte programming. Published: June, 2019 Abstract:
p63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodim... Read more »
TF-ChIP Method for Tissue-Specific Gene Targets. Published: March, 2019 Abstract:
Chromatin immunoprecipitation (ChIP) is an assay developed in order to define the dynamic nature of transcription processes. This method has been widely employed to identify methylated and acetylated DNA sequences in a variety of organs both in an... Read more »
Nuclear fate of yeast snoRNA is determined by co-transcriptional Rnt1 cleavage Published: May, 2018 Abstract:
Small nucleolar RNA (snoRNA) are conserved and essential non-coding RNA that are transcribed by RNA Polymerase II (Pol II). Two snoRNA classes, formerly distinguished by their structure and ribonucleoprotein composition, act as guide RNA to target... Read more »
MYCN acts as a direct co-regulator of p53 in MYCN amplified neuroblastoma Published: April, 2018 Abstract:
The MYC oncogenes and p53 have opposing yet interrelated roles in normal development and tumorigenesis. How MYCN expression alters the biology and clinical responsiveness of pediatric neuroblastoma remains poorly defined. Neuroblastoma is p53 wild... Read more »
Analysis of Meiotic Double-Strand Break Initiation in Mammals Published: March, 2018 Abstract:
The repair of programmed DNA double-strand breaks (DSBs) physically tethers homologous chromosomes in meiosis to allow for accurate segregation through meiotic cell divisions. This process, known as recombi... Read more »
Super enhancer associated RAI14 is a new potential biomarker in lung adenocarcinoma Published: December, 2017 Abstract:
Tyrosine kinase inhibitors (TKIs) are widely used to treat lung adenocarcinoma patients with EGFR mutations or ALK-fusions. However, patients with wild-type genes or TKIs-resistant mutations lack effective therapeutic targets. Extensive studies re... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 (... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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, ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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 ... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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., ... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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) ... Read more »
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 ... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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,... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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. ... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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 ... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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... Read more »
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 ... Read more »
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... Read more »