Diagenode

Chromatin Shearing

1452 publications found.

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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin.
Published: April, 2015

Abstract: Heterochromatic domains are enriched with repressive histone marks, including histone H3 lysine 9 methylation, written by lysine methyltransferases (KMTs). The pre-replication complex protein, origin recognition complex-associated (ORCA/LRWD1), pr...
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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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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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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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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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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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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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Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter.
Published: April, 2015

Abstract: The serine/threonine kinase glycogen synthase kinase-3 (GSK3) plays an important role in balancing pro- and anti-inflammatory cytokines. We have examined the role of GSK3 in production of IL-10 by subsets of CD4(+) T helper cells. Treatment of nai...
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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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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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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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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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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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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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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 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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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 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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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-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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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A novel protein, CHRONO, functions as a core component of the mammalian circadian clock.
Published: April, 2014

Abstract: Circadian rhythms are controlled by a system of negative and positive genetic feedback loops composed of clock genes. Although many genes have been implicated in these feedback loops, it is unclear whether our current list of clock genes is exhaus...
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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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Farnesoid X receptor directly regulates xenobiotic detoxification genes in the long-lived Little mice.
Published: September, 2013

Abstract: Activation of xenobiotic metabolism pathways has been linked to lifespan extension in different models of aging. However, the mechanisms underlying activation of xenobiotic genes remain largely unknown. Here we showed that although farnesoid X rec...
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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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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Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.
Published: June, 2013

Abstract: The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgeni...
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The Glucocorticoid Receptor and KLF15 Regulate Gene Expression Dynamics and Integrate Signals through Feed-Forward Circuitry.
Published: June, 2013

Abstract: The glucocorticoid receptor (GR) regulates adaptive transcriptional programs that alter metabolism in response to stress. Network properties that allow GR to tune gene expression to match specific physiologic demands are poorly understood. We anal...
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Functional dissection of the PROPEP2 and PROPEP3 promoters reveals the importance of WRKY factors in mediating microbe-associated molecular pattern-induced expression.
Published: June, 2013

Abstract: · In Arabidopsis thaliana, small peptides (AtPeps) encoded by PROPEP genes act as damage-associated molecular patterns (DAMPs) that are perceived by two leucine-rich repeat receptor kinases, PEPR1 and PEPR2, to amplify defense responses. In partic...
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A new strategy for selective targeting of progesterone receptor with passive antagonists.
Published: June, 2013

Abstract: Currently available progesterone (P4) receptor (PR) antagonists, such as mifepristone (RU486), lack specificity and display partial agonist properties, leading to potential drawbacks in their clinical use. Recent x-ray crystallographic studies hav...
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Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis.
Published: June, 2013

Abstract: Hox genes encode transcription factors governing complex developmental processes in several organs. A subset of Hox genes are expressed in the developing lung. Except for Hoxa5, the lack of overt lung phenotype in single mutants suggests that Hox ...
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HOXA13 regulates Aldh1a2 expression in the autopod to facilitate interdigital programmed cell death.
Published: June, 2013

Abstract: Background: Retinoic acid (RA), plays an essential role in the growth and patterning of vertebrate limb. While the developmental processes regulated by RA are well understood, little is known about the transcriptional mechanisms required to precis...
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A novel role for Sem1 and TREX-2 in transcription involves their impact on recruitment and H2B deubiquitylation activity of SAGA.
Published: June, 2013

Abstract: Transcription and mRNA export are linked processes. However, the molecular mechanisms of this coordination are not clear. Sus1 (hENY2) participates in this coordination as part of two protein complexes: SAGA, a transcriptional co-activator; TREX-2...
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Histone acetyl transferase 1 is essential for mammalian development, genome stability, and the processing of newly synthesized histones H3 and H4.
Published: June, 2013

Abstract: Histone acetyltransferase 1 is an evolutionarily conserved type B histone acetyltransferase that is thought to be responsible for the diacetylation of newly synthesized histone H4 on lysines 5 and 12 during chromatin assembly. To understand the fu...
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Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection.
Published: June, 2013

Abstract: Although vitamin D deficiency is a common feature among patients presenting with active tuberculosis, the full scope of vitamin D action during Mycobacterium tuberculosis (Mtb) infection is poorly understood. As macrophages are the primary site of...
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Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo.
Published: May, 2013

Abstract: Bcl11a is a transcription factor known to regulate lymphoid and erythroid development. Recent bioinformatic analysis of global gene expression patterns has suggested a role for Bcl11a in the development of dendritic cell (DC) lineages. We tested t...
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KDM4B is a Master Regulator of the Estrogen Receptor Signalling Cascade.
Published: May, 2013

Abstract: The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER ...
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CREB phosphorylation regulates striatal transcriptional responses in the self-administration model of methamphetamine addiction in the rat.
Published: May, 2013

Abstract: Neuroplastic changes in the dorsal striatum participate in the transition from casual to habitual drug use and might play a critical role in the development of methamphetamine (METH) addiction. We examined the influence of METH self-administration...
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Recombination-Induced Tag Exchange (RITE) Cassette Series to Monitor Protein Dynamics in Saccharomyces cerevisiae.
Published: May, 2013

Abstract: Proteins are not static entities. They are highly mobile, and their steady-state levels are achieved by a balance between ongoing synthesis and degradation. The dynamic properties of a protein can have important consequences for its function. For ...
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Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis.
Published: May, 2013

Abstract: Maintaining proper mRNA levels is a key aspect in the regulation of gene expression. The balance between mRNA synthesis and decay determines these levels. We demonstrate that most yeast mRNAs are degraded by the cytoplasmic 5'-to-3' pathway (the "...
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Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata.
Published: May, 2013

Abstract: Mutations in BCOR (Bcl6 corepressor) are found in patients with oculo-facio-cardio-dental (OFCD) syndrome, a congenital disorder affecting visual system development, and loss-of-function studies in zebrafish and Xenopus demonstrate a role for Bcor...
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Ptc6 Is required for proper rapamycin-induced down-regulation of the genes coding for ribosomal and rRNA processing proteins in S. cerevisiae.
Published: May, 2013

Abstract: Ptc6 is one of the seven components (Ptc1-Ptc7) of the protein phosphatase 2C family in the yeast Saccharomyces cerevisiae. In contrast to other type 2C phosphatases, the cellular role of this isoform is poorly understood. We present here a compre...
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The co-repressor SMRT delays DNA damage-induced caspase activation by repressing pro-apoptotic genes and modulating the dynamics of checkpoint kinase 2 activation.
Published: May, 2013

Abstract: Checkpoint kinase 2 (Chk2) is a major regulator of DNA damage response and can induce alternative cellular responses: cell cycle arrest and DNA repair or programmed cell death. Here, we report the identification of a new role of Chk2 in transcript...
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Overexpression of facioscapulohumeral muscular dystrophy region gene 1 causes primary defects in myogenic stem cells.
Published: May, 2013

Abstract: Overexpression of facioscapulohumeral muscular dystrophy region gene 1 (FRG1) in mice, frogs and worms leads to muscular and vascular abnormalities. Nevertheless, the mechanism that follows FRG1 overexpression and finally leads to muscular defects...
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Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells
Published: May, 2013

Abstract: While the Polycomb complex is known to regulate cell identity in ES cells, its role in controlling tissue-specific stem cells is not well understood. Here we show that removal of Ezh1 and Ezh2, key Polycomb subunits, from mouse skin results in a m...
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SUMOylation of the Farnesoid X Receptor (FXR) Regulates the Expression of FXR Target Genes.
Published: May, 2013

Abstract: The farnesoid X receptor (FXR) belongs to a family of ligand-activated transcription factors that regulate many aspects of metabolism including bile acid homeostasis. Here we show that FXR is covalently modified by the small ubiquitin-like modifie...
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Androgen-responsive Serum Response Factor target genes regulate prostate cancer cell migration.
Published: May, 2013

Abstract: Progression of prostate cancer (CaP) relies on androgen receptor (AR) signaling, but AR-dependent events that underlie the lethal phenotype remain unknown. Recently, an indirect mechanism of androgen action in which effects of AR on CaP cells are ...
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Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs.
Published: May, 2013

Abstract: Alterations of symbiosis between microbiota and intestinal epithelial cells (IEC) are associated with intestinal and systemic pathologies. Interactions between bacterial products (MAMPs) and Toll-like receptors (TLRs) are known to be mandatory for...
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LIN9, a subunit of the DREAM complex, regulates mitotic gene expression and proliferation of embryonic stem cells.
Published: May, 2013

Abstract: The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vi...
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Sirt1 ablation promotes stress-induced loss of epigenetic and genomic hematopoietic stem and progenitor cell maintenance.
Published: May, 2013

Abstract: The (histone) deacetylase Sirt1 is a mediator of genomic and epigenetic maintenance, both of which are critical aspects of stem cell homeostasis and tightly linked to their functional decline in aging and disease. We show that Sirt1 ablation in ad...
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Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality.
Published: May, 2013

Abstract: Studies of post-mortem brains from Alzheimer disease patients suggest that oxidative damage induced by mitochondrial amyloid β (mitAβ) accumulation is associated with mitochondrial dysfunction. However, the regulation of mitAβ metabolism is unknow...
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Estrogen-dependent dynamic profile of eNOS-DNA associations in prostate cancer.
Published: May, 2013

Abstract: In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ERβ) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remo...
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Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation.
Published: May, 2013

Abstract: Growing evidence suggests epigenetic alteration is involved during the development and progression of prostate cancer. Previously, we found Nrf2, a key regulator of cellular antioxidant defense systems, was silenced through epigenetic mechanism du...
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Epigenetic regulation of cholinergic receptor M1 (CHRM1) by histone H3K9me3 impairs Ca(2+) signaling in Huntington's disease.
Published: May, 2013

Abstract: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded trinucleotide CAG repeat in the gene coding for huntingtin. Deregulation of chromatin remodeling is linked to the pathogenesis of HD but the mechani...
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Developmentally programmed 3' CpG island methylation confers tissue- and cell-type-specific transcriptional activation.
Published: May, 2013

Abstract: During development, a small but significant number of CpG islands (CGIs) become methylated. The timing of developmentally programmed CGI methylation and associated mechanisms of transcriptional regulation during cellular differentiation, however, ...
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Epigenetic changes in renal genes dysregulated in mouse and rat models of type 1 diabetes.
Published: May, 2013

Abstract: Epigenetic processes are increasingly being recognized as factors in the pathophysiology of diabetes complications, but few chromatin studies have been done in diabetic nephropathy (DN). We hypothesized that changes in mRNA expression of DN-relate...
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G9a is transactivated by C/EBPβ to facilitate mitotic clonal expansion during 3T3-L1 preadipocyte differentiation.
Published: May, 2013

Abstract: In 3T3-L1 preadipocyte differentiation, the CCAAT/enhancer-binding protein-β (C/EBPβ) is an important early transcription factor that activates cell cycle genes during mitotic clonal expansion (MCE), sequentially activating peroxisome proliferator...
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The genome of the platyfish, Xiphophorus maculatus, provides insights into evolutionary adaptation and several complex traits.
Published: May, 2013

Abstract: Several attributes intuitively considered to be typical mammalian features, such as complex behavior, live birth and malignant disease such as cancer, also appeared several times independently in lower vertebrates. The genetic mechanisms underlyin...
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A Common histone modification code on C4 genes in maize and its conservation in Sorghum and Setaria italica.
Published: May, 2013

Abstract: C4 photosynthesis evolved more than 60 times independently in different plant lineages. Each time, multiple genes were recruited into C4 metabolism. The corresponding promoters acquired new regulatory features such as high expression, light induct...
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Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment.
Published: May, 2013

Abstract: How hematopoietic stem cells (HSCs) coordinate the regulation of opposing cellular mechanisms such as self-renewal and differentiation commitment remains unclear. Here we identified the transcription factor and chromatin remodeler Satb1 as a criti...
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Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells.
Published: May, 2013

Abstract: Loss of nuclear progesterone receptors (PR) and low circulating progesterone levels are associated with increased ovarian cancer (OC) risk. However, PR are abundantly expressed in a significant percentage of serous and endometrioid ovarian tumors;...
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Heterochromatin protein 1 promotes self-renewal and triggers regenerative proliferation in adult stem cells
Published: April, 2013

Abstract: Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expressio...
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Coordinate changes in histone modifications, mRNA levels, and metabolite profiles in clonal INS-1 832/13 β-cells accompany functional adaptations to lipotoxicity.
Published: April, 2013

Abstract: Lipotoxicity is a presumed pathogenetic process whereby elevated circulating and stored lipids in type 2 diabetes cause pancreatic β-cell failure. To resolve the underlying molecular mechanisms, we exposed clonal INS-1 832/13 β-cells to palmitate ...
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Balancing of histone H3K4 methylation states by the Kdm5c/SMCX histone demethylase modulates promoter and enhancer function.
Published: April, 2013

Abstract: The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes such as enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but ...
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A proteomic characterization of factors enriched at nascent DNA molecules.
Published: April, 2013

Abstract: DNA replication is facilitated by multiple factors that concentrate in the vicinity of replication forks. Here, we developed an approach that combines the isolation of proteins on nascent DNA chains with mass spectrometry (iPOND-MS), allowing a co...
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Placing the HIRA histone chaperone complex in the chromatin landscape.
Published: April, 2013

Abstract: The HIRA chaperone complex, comprised of HIRA, UBN1, and CABIN1, collaborates with histone-binding protein ASF1a to incorporate histone variant H3.3 into chromatin in a DNA replication-independent manner. To better understand HIRA's function and m...
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A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response.
Published: April, 2013

Abstract: Liver fibrosis is a reversible wound-healing response involving TGFβ1/SMAD activation of hepatic stellate cells (HSCs). It results from excessive deposition of extracellular matrix components and can lead to impairment of liver function. Here, we ...
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Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation.
Published: April, 2013

Abstract: How the transcription repressing complex Polycomb interacts with transcriptional regulators at housekeeping genes in somatic cells is not well understood. By exploiting a CpG island (CGI) point mutation causing a Mendelian disease, we show that DN...
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The response of human macrophages to β-glucans depends on the inflammatory milieu.
Published: April, 2013

Abstract: BACKGROUND: β-glucans are fungal cell wall components that bind to the C-type lectin-like receptor dectin-1. Polymorphisms of dectin-1 gene are associated with susceptibility to invasive fungal infection and medically refractory ulcerative colitis...
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Hypersensitive site 6 of the Th2 locus control region is essential for Th2 cytokine expression.
Published: April, 2013

Abstract: The T helper type 2 (Th2) cytokine genes Il4, Il5, and Il13 are contained within a 140-kb region of mouse chromosome 11 and their expression is controlled by a locus control region (LCR) embedded within this locus. The LCR is composed of a number ...
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The developmental epigenomics toolbox: ChIP-seq and MethylCap-seq profiling of early zebrafish embryos.
Published: April, 2013

Abstract: Genome-wide profiling of DNA methylation and histone modifications answered many questions as to how the genes are regulated on a global scale and what their epigenetic makeup is. Yet, little is known about the function of these marks during early...
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Estradiol represses the G(D3) synthase gene ST8SIA1 expression in human breast cancer cells by preventing NFκB binding to ST8SIA1 promoter.
Published: April, 2013

Abstract: Recent data have underlined a possible role of G(D3) synthase (GD3S) and complex gangliosides in Estrogen Receptor (ER) negative breast cancer progression. Here, we describe the main transcript of the GD3S coding gene ST8SIA1 expressed in breast t...
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The histone demethylase Jmjd3 sequentially associates with the transcription factors Tbx3 and Eomes to drive endoderm differentiation
Published: April, 2013

Abstract: Stem cell differentiation depends on transcriptional activation driven by lineage-specific regulators as well as changes in chromatin organization. However, the coordination of these events is poorly understood. Here, we show that T-box proteins t...
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Exit from pluripotency is gated by intracellular redistribution of the bHLH transcription factor Tfe3.
Published: April, 2013

Abstract: Factors that sustain self-renewal of mouse embryonic stem cells (ESCs) are well described. In contrast, the machinery regulating exit from pluripotency is ill defined. In a large-scale small interfering RNA (siRNA) screen, we found that knockdown ...
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Methylation-dependent and -independent genomic targeting principles of the MBD protein family.
Published: April, 2013

Abstract: To gain insight into the cellular readout of DNA methylation, we established a strategy for systematically profiling the genome-wide distribution of chromatin-interacting factors. This enabled us to create genomic maps for the methyl-CpG-binding d...
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Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance
Published: April, 2013

Abstract: Epigenetically regulated heterochromatin domains govern essential cellular activities. A key feature of heterochromatin domains is the presence of hypoacetylated nucleosomes, which are methylated on lysine 9 of histone H3 (H3K9me). Here, we invest...
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Acyl-CoA synthetase 1 is induced by Gram-negative bacteria and lipopolysaccharide and is required for phospholipid turnover in stimulated macrophages.
Published: April, 2013

Abstract: The enzyme acyl-CoA synthetase 1 (ACSL1) is induced by peroxisome proliferator-activated receptor α (PPARα) and PPARγ in insulin target tissues, such as skeletal muscle and adipose tissue, and plays an important role in β-oxidation in these tissue...
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Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers.
Published: April, 2013

Abstract: Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in...
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Utx is required for proper induction of ectoderm and mesoderm during differentiation of embryonic stem cells.
Published: April, 2013

Abstract: Embryonic development requires chromatin remodeling for dynamic regulation of gene expression patterns to ensure silencing of pluripotent transcription factors and activation of developmental regulators. Demethylation of H3K27me3 by the histone de...
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Akt kinase targets the association of CBP with histone H3 to regulate the acetylation of lysine K18.
Published: April, 2013

Abstract: CREB binding protein (CBP) is an acetyltransferase that plays an important role in many biological processes. Here, we show that Akt phosphorylates CBP at threonine 1871 and suppresses its acetyltransferase activity by impeding the binding of CBP ...
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Genome-wide analysis of LXRα activation reveals new transcriptional networks in human atherosclerotic foam cells.
Published: April, 2013

Abstract: Increased physiological levels of oxysterols are major risk factors for developing atherosclerosis and cardiovascular disease. Lipid-loaded macrophages, termed foam cells, are important during the early development of atherosclerotic plaques. To p...
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A systemic transcriptome analysis reveals the regulation of neural stem cell maintenance by an E2F1-miRNA feedback loop.
Published: April, 2013

Abstract: Stem cell fate decisions are controlled by a molecular network in which transcription factors and miRNAs are of key importance. To systemically investigate their impact on neural stem cell (NSC) maintenance and neuronal commitment, we performed a ...
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Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes.
Published: April, 2013

Abstract: Death domain-associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPas...
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Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11.
Published: April, 2013

Abstract: ZNF143 is a zinc-finger protein involved in the transcriptional regulation of both coding and non-coding genes from polymerase II and III promoters. Our study deciphers the genome-wide regulatory role of ZNF143 in relation with the two previously ...
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Multiple functions of Kip-related protein5 connect endoreduplication and cell elongation.
Published: April, 2013

Abstract: Despite considerable progress in our knowledge regarding the cell cycle inhibitor of the Kip-related protein (KRP) family in plants, less is known about the coordination of endoreduplication and cell differentiation. In animals, the role of cyclin...
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A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells.
Published: April, 2013

Abstract: PTEN is a tumor-suppressor gene that has been shown to be under the regulatory control of a PTEN pseudogene expressed noncoding RNA, PTENpg1. Here, we characterize a previously unidentified PTENpg1-encoded antisense RNA (asRNA), which regulates PT...
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Epigenetic and molecular signature of human umbilical cord blood-derived neural stem cell (HUCB-NSC) neuronal differentiation.
Published: April, 2013

Abstract: In the context of cell therapy, the epigenetic status of core stemness transcription factor (STF) genes regulating the cell proliferation/differentiation program is of primary interest. Our results confirmed that in vitro differentiation of the um...
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Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the In Cis downregulation of a gene cluster that targets NF-kB.
Published: April, 2013

Abstract: Non-coding RNAs are much more common than previously thought. However, for the vast majority of non-coding RNAs, the cellular function remains enigmatic. The two long non-coding RNA (lncRNA) genes DLEU1 and DLEU2 map to a critical region at chromo...
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Intrinsic epigenetic regulation of the D4Z4 macrosatellite repeat in a transgenic mouse model for FSHD.
Published: April, 2013

Abstract: Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in e...
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Multiple IRF- and NFkB-sites cooperate in mediating cell type- and maturation-specific activation of the human CD83 promoter in dendritic cells.
Published: April, 2013

Abstract: CD83 is one of the best-known surface marker for fully mature dendritic cells (DCs) and its cell type- and maturation-specific regulation makes the CD83 promoter an interesting tool for the genetic modulation of DCs. To determine the mechanisms re...
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Single-cell dynamics of genome-nuclear lamina interactions.
Published: March, 2013

Abstract: The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs...
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The role of proteasome beta subunits in gastrin-mediated transcription of plasminogen activator inhibitor-2 and regenerating protein1.
Published: March, 2013

Abstract: The hormone gastrin physiologically regulates gastric acid secretion and also contributes to maintaining gastric epithelial architecture by regulating expression of genes such as plasminogen activator inhibitor 2 (PAI-2) and regenerating protein 1...
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Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation.
Published: March, 2013

Abstract: Type II DNA topoisomerases catalyse DNA double-strand cleavage, passage and re-ligation to effect topological changes. There is considerable interest in elucidating topoisomerase II roles, particularly as these proteins are targets for anti-cancer...
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Epigenetic reactivation of Nrf2 in murine prostate cancer TRAMP C1 cells by natural phytochemicals Z-ligustilide and Radix angelica sinensis via promoter CpG demethylation.
Published: March, 2013

Abstract: Cancer development has been linked to epigenetic modifications of cancer oncogenes and tumor suppressor genes; in advanced metastatic cancers, severe epigenetic modifications are present. We previously demonstrated that the progression of prostate...
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The BEN domain is a novel sequence-specific DNA-binding domain conserved in neural transcriptional repressors.
Published: March, 2013

Abstract: We recently reported that Drosophila Insensitive (Insv) promotes sensory organ development and has activity as a nuclear corepressor for the Notch transcription factor Suppressor of Hairless [Su(H)]. Insv lacks domains of known biochemical functio...
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Fission yeast CSL proteins function as transcription factors.
Published: March, 2013

Abstract: BACKGROUND: Transcription factors of the CSL (CBF1/RBP-Jk/Suppressor of Hairless/LAG-1) family are key regulators of metazoan development and function as the effector components of the Notch receptor signalling pathway implicated in various cell f...
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PRC1 coordinates timing of sexual differentiation of female primordial germ cells.
Published: March, 2013

Abstract: In mammals, sex differentiation of primordial germ cells (PGCs) is determined by extrinsic cues from the environment. In mouse female PGCs, expression of stimulated by retinoic acid gene 8 (Stra8) and meiosis are induced in response to retinoic ac...
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Shift from extracellular signal-regulated kinase to AKT/cAMP response element-binding protein pathway increases survival-motor-neuron expression in spinal-muscular-atrophy-like mice and patient cells.
Published: March, 2013

Abstract: Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one of the leading genetic causes of death in childhood. SM...
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Epigenetic hierarchy within the MAGEA1 cancer-germline gene: promoter DNA methylation dictates local histone modifications.
Published: March, 2013

Abstract: Gene MAGEA1 belongs to a group of human germline-specific genes that rely on DNA methylation for repression in somatic tissues. Many of these genes, termed cancer-germline (CG) genes, become demethylated and activated in a wide variety of tumors, ...
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Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination.
Published: March, 2013

Abstract: The pathogenic sequelae of BRCA1 mutation in human and mouse cells are mitigated by concomitant deletion of 53BP1, which binds histone H4 dimethylated at Lys20 (H4K20me2) to promote nonhomologous end joining, suggesting that a balance between BRCA...
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H2A.Z and H2B.Z double-variant nucleosomes define intergenic regions and dynamically occupy var gene promoters in the malaria parasite Plasmodium falciparum.
Published: March, 2013

Abstract: Histone variants are important components of eukaryotic chromatin and can alter chromatin structure to confer specialized functions. H2B variant histones are rare in nature but have evolved independently in the phyla Apicomplexa and Trypanasomatid...
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Myod and H19-Igf2 locus interactions are required for diaphragm formation in the mouse.
Published: March, 2013

Abstract: The myogenic regulatory factor Myod and insulin-like growth factor 2 (Igf2) have been shown to interact in vitro during myogenic differentiation. In order to understand how they interact in vivo, we produced double-mutant mice lacking both the Myo...
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Chromatin immunoprecipitation of adult murine cardiomyocytes.
Published: March, 2013

Abstract: This unit describes a streamlined two-step protocol for the isolation of adult murine cardiomyocytes with subsequent Chromatin ImmunoPrecipitation (ChIP). Isolation and culturing of cardiomyocytes is a delicate process and the protocol presented h...
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Genome-wide control of RNA polymerase II activity by cohesin.
Published: March, 2013

Abstract: Cohesin is a well-known mediator of sister chromatid cohesion, but it also influences gene expression and development. These non-canonical roles of cohesin are not well understood, but are vital: gene expression and development are altered by mode...
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Activating RNAs associate with Mediator to enhance chromatin architecture and transcription.
Published: February, 2013

Abstract: Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epi...
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H3K4me3 interactions with TAF3 regulate preinitiation complex assembly and selective gene activation.
Published: February, 2013

Abstract: Histone modifications regulate chromatin-dependent processes, yet the mechanisms by which they contribute to specific outcomes remain unclear. H3K4me3 is a prominent histone mark that is associated with active genes and promotes transcription thro...
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SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.
Published: February, 2013

Abstract: SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show ...
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Polycomb domain formation depends on short and long distance regulatory cues.
Published: February, 2013

Abstract: BACKGROUND: Polycomb group (PcG) proteins dynamically define cellular identities through the epigenetic repression of key developmental genes. In Drosophila, cis-regulatory regions termed PcG response elements (PREs) act as nucleation sites for Pc...
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Inhibition of neural crest formation by Kctd15 involves regulation of transcription factor AP-2.
Published: February, 2013

Abstract: The neural crest develops in vertebrate embryos within a discrete domain at the neural plate boundary and eventually gives rise to a migrating population of cells that differentiate into a multitude of derivatives. We have shown that the broad-com...
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ARCH domain of XPD, an anchoring platform for CAK that conditions TFIIH DNA repair and transcription activities.
Published: February, 2013

Abstract: The xeroderma pigmentosum group D (XPD) helicase is a subunit of transcription/DNA repair factor, transcription factor II H (TFIIH) that catalyzes the unwinding of a damaged DNA duplex during nucleotide excision repair. Apart from two canonical he...
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Multiple roles for Piwi in silencing Drosophila transposons.
Published: February, 2013

Abstract: Silencing of transposons in the Drosophila ovary relies on three Piwi family proteins--Piwi, Aubergine (Aub), and Ago3--acting in concert with their small RNA guides, the Piwi-interacting RNAs (piRNAs). Aub and Ago3 are found in the germ cell cyto...
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Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer.
Published: February, 2013

Abstract: Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates ch...
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Krüppel-like factor 2 is required for normal mouse cardiac development.
Published: February, 2013

Abstract: Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure an...
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Identification of thyroid hormone response elements in vivo using mice expressing a tagged thyroid hormone receptor alpha 1.
Published: February, 2013

Abstract: Thyroid hormone receptor alpha 1 (TRα1) is well recognized for its importance in brain development. However, due to the difficulties in predicting thyroid hormone response elements (TREs) in silico and the lack of suitable antibodies against TRα1 ...
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SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation.
Published: February, 2013

Abstract: The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of ...
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Direct molecular regulation of the myogenic determination gene Myf5 by Pax3, with modulation by Six1/4 factors, is exemplified by the -111kb-Myf5 enhancer.
Published: February, 2013

Abstract: The Myf5 gene plays an important role in myogenic determination during mouse embryo development. Multiple genomic regions of the Mrf4-Myf5 locus have been characterized as enhancer sequences responsible for the complex spatiotemporal expression of...
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Linking proteomic and transcriptional data through the interactome and epigenome reveals a map of oncogene-induced signaling.
Published: February, 2013

Abstract: Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study eac...
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Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.
Published: February, 2013

Abstract: AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understa...
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Bifurcation of Arabidopsis NLR immune signaling via Ca²⁺-dependent protein kinases.
Published: January, 2013

Abstract: Nucleotide-binding domain leucine-rich repeat (NLR) protein complexes sense infections and trigger robust immune responses in plants and humans. Activation of plant NLR resistance (R) proteins by pathogen effectors launches convergent immune respo...
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The Function of the Conserved Regulatory Element within the Second Intron of the Mammalian Csf1r Locus
Published: January, 2013

Abstract: The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), i...
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Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression
Published: January, 2013

Abstract: E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. ...
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Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2.
Published: January, 2013

Abstract: The mammary epithelium is a dynamic, highly hormone-responsive tissue. To explore chromatin modifications underlying its lineage specification and hormone responsiveness, we determined genome-wide histone methylation profiles of mammary epithelial...
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Specificity and Function of Archaeal DNA Replication Initiator Proteins.
Published: January, 2013

Abstract: Chromosomes with multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea. All eukaryal nuclear replication origins are defined by the origin recognition complex (ORC) that recruits the replicative helicase MCM(2-7) via Cdc6 ...
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Identification of Transcription factors and Co-activators Affected by Dibutyl Phthalate Interactions in Fetal Rat Testes.
Published: January, 2013

Abstract: Previous analysis of in utero dibutylphthalate (DBP)-exposed fetal rat testes indicated that DBP's anti-androgenic effects were mediated in part by indirect inhibition of SF1 suggesting that PPARα might be involved through coactivtor (CBP) sequest...
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Notch pathway activation targets AML-initiating cell homeostasis and differentiation.
Published: January, 2013

Abstract: Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neo...
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Cell Cycle-Dependent Recruitment of Polycomb Proteins to the ASNS Promoter Counteracts C/ebp-Mediated Transcriptional Activation in Bombyx mori
Published: January, 2013

Abstract: Epigenetic modifiers and transcription factors contribute to developmentally programmed gene expression. Here, we establish a functional link between epigenetic regulation by Polycomb group (PcG) proteins and transcriptional regulation by C/ebp th...
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Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.
Published: January, 2013

Abstract: How a more plastic chromatin state is maintained and reversed during development is unknown. Heterochromatin-mediated silencing of repetitive elements occurs in differentiated cells. Here, we used repetitive elements, including retrotransposons, a...
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Bookmarking by specific and nonspecific binding of FoxA1 pioneer factor to mitotic chromosomes.
Published: January, 2013

Abstract: While most transcription factors exit the chromatin during mitosis and the genome becomes silent, a subset of factors remains and "bookmarks" genes for rapid reactivation as cells progress through the cell cycle. However, it is unknown whether suc...
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MeCP2 modulates gene expression pathways in astrocytes.
Published: January, 2013

Abstract: ABSTRACT: BACKGROUND: Mutations in MECP2 encoding methyl-CpG-binding protein 2 (MeCP2) cause the X-linked neurodevelopmental disorder Rett syndrome. Rett syndrome patients exhibit neurological symptoms that include irregular breathing, impaired mo...
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Valproic acid inhibits the proliferation of cancer cells by re-expressing cyclin D2.
Published: January, 2013

Abstract: In this study, primary murine prostate cancer (PCa) cells were derived using the well-established TRAMP model (transgenic adenocarcinoma mouse prostate). These PCa cells were treated with the histone deacetylase inhibitor (HDACi), valproic acid (V...
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An in vivo hypoxia metagene identifies the novel hypoxia inducible factor target gene SLCO1B3
Published: January, 2013

Abstract: A hypoxia-associated gene signature (metagene) was previously derived via in vivo data-mining. In this study, we aimed to investigate whether this approach could identify novel hypoxia regulated genes. From an initial list of nine genes, three wer...
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SIRT1 Positively Regulates Breast Cancer Associated Human Aromatase (CYP19A1) Expression.
Published: January, 2013

Abstract: Breast cancer remains one of the leading causes of death in women diagnosed with cancer. In breast cancer, aberrant expression of the CYP19A1 gene, which encodes the aromatase enzyme, contributes to increased intratumoral levels of estradiol. Rega...
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Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment.
Published: January, 2013

Abstract: Long noncoding RNAs (lncRNAs) are often expressed in a development-specific manner, yet little is known about their roles in lineage commitment. Here, we identified Braveheart (Bvht), a heart-associated lncRNA in mouse. Using multiple embryonic st...
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In Vivo Epigenomic Profiling of Germ Cells Reveals Germ Cell Molecular Signatures.
Published: January, 2013

Abstract: The limited number of in vivo germ cells poses an impediment to genome-wide studies. Here, we applied a small-scale chromatin immunoprecipitation sequencing (ChIP-seq) method on purified mouse fetal germ cells to generate genome-wide maps of four ...
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RUNX1 Is a Key Target in t(4;11) Leukemias that Contributes to Gene Activation through an AF4-MLL Complex Interaction.
Published: January, 2013

Abstract: The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in human...
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Dual function of MIPS1 as a metabolic enzyme and transcriptional regulator.
Published: January, 2013

Abstract: Because regulation of its activity is instrumental either to support cell proliferation and growth or to promote cell death, the universal myo-inositol phosphate synthase (MIPS), responsible for myo-inositol biosynthesis, is a critical enzyme of p...
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The SIRT1 Modulators AROS and DBC1 Regulate HSF1 Activity and the Heat Shock Response
Published: January, 2013

Abstract: The heat shock response, the cellular response to protein damaging stress, is critical in maintaining proteostasis. The heat shock response is regulated by the transcription factor HSF1, which is activated upon heat shock and other stresses to ind...
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Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation
Published: January, 2013

Abstract: Establishment of oligodendrocyte identity is crucial for subsequent events of myelination in the CNS. Here, we demonstrate that activation of ATP-dependent SWI/SNF chromatin-remodeling enzyme Smarca4/Brg1 at the differentiation onset is necessary ...
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Myb-domain protein Teb1 controls histone levels and centromere assembly in fission yeast.
Published: January, 2013

Abstract: The TTAGGG motif is common to two seemingly unrelated dimensions of chromatin function-the vertebrate telomere repeat and the promoter regions of many Schizosaccharomyces pombe genes, including all of those encoding canonical histones. The essenti...
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Pre-mRNA Splicing Is a Determinant of Nucleosome Organization
Published: January, 2013

Abstract: Chromatin organization affects alternative splicing and previous studies have shown that exons have increased nucleosome occupancy compared with their flanking introns. To determine whether alternative splicing affects chromatin organization we de...
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Dynamic Chromatin Remodeling Mediated by Polycomb Proteins Orchestrates Pancreatic Differentiation of Human Embryonic Stem Cells.
Published: January, 2013

Abstract: Embryonic development is characterized by dynamic changes in gene expression, yet the role of chromatin remodeling in these cellular transitions remains elusive. To address this question, we profiled the transcriptome and select chromatin modifica...
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Histone methyltransferase MLL3 contributes to genome-scale circadian transcription.
Published: January, 2013

Abstract: Daily cyclical expression of thousands of genes in tissues such as the liver is orchestrated by the molecular circadian clock, the disruption of which is implicated in metabolic disorders and cancer. Although we understand much about the circadian...
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Direct Transcriptional Regulation of Human Hepatic Cytochrome P450 3A4 (CYP3A4) by Peroxisome Proliferator-Activated Receptor Alpha (PPARα).
Published: January, 2013

Abstract: The nuclear receptor peroxisome proliferator-activated receptor (PPAR)α is primarily known as a regulator of fatty acid metabolism, energy balance, and inflammation, but there is evidence suggesting a wider role in regulating biotransformation of ...
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Identification and analysis of the proximal promoters of microRNA genes in Arabidopsis.
Published: January, 2013

Abstract: Endogenous microRNAs (miRNAs) modulate gene expression at the post-transcription level. In plants, a vast majority of MIR genes are thought to be transcribed by RNA Polymerase II (Pol II). However, promoter organization is currently unknown for mo...
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The WalRK (YycFG) and σ(I) RsgI regulators cooperate to control CwlO and LytE expression in exponentially growing and stressed Bacillus subtilis cells.
Published: January, 2013

Abstract: The WalRK (YycFG) two-component system co-ordinates cell wall metabolism with growth by regulating expression of autolysins and proteins that modulate autolysin activity. Here we extend its role in cell wall metabolism by showing that WalR binds t...
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Bridging Decapentaplegic and Wingless signaling in Drosophila wings through repression of naked cuticle by Brinker.
Published: January, 2013

Abstract: Wnts and bone morphogenetic proteins (BMPs) are signaling elements that are crucial for a variety of events in animal development. In Drosophila, Wingless (Wg, a Wnt ligand) and Decapentaplegic (Dpp, a BMP homolog) are thought to function through ...
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ATR-like kinase Mec1 facilitates both chromatin accessibility at DNA replication forks and replication fork progression during replication stress.
Published: January, 2013

Abstract: Faithful DNA replication is essential for normal cell division and differentiation. In eukaryotic cells, DNA replication takes place on chromatin. This poses the critical question as to how DNA replication can progress through chromatin, which is ...
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Poised RNA Polymerase II Changes over Developmental Time and Prepares Genes for Future Expression.
Published: December, 2012

Abstract: Poised RNA polymerase II (Pol II) is predominantly found at developmental control genes and is thought to allow their rapid and synchronous induction in response to extracellular signals. How the recruitment of poised RNA Pol II is regulated durin...
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The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation.
Published: December, 2012

Abstract: Enhancers play a central role in precisely regulating the expression of developmentally regulated genes. However, the machineries required for enhancer-promoter communication have remained largely unknown. We have found that Ell3, a member of the ...
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Epigenetic Regulation of Nestin Expression During Neurogenic Differentiation of Adipose Tissue Stem Cells.
Published: December, 2012

Abstract: Adipose-tissue-derived stem cells (ASCs) have received considerable attention due to their easy access, expansion potential, and differentiation capacity. ASCs are believed to have the potential to differentiate into neurons. However, the mechanis...
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A Molecular Roadmap of Reprogramming Somatic Cells into iPS Cells.
Published: December, 2012

Abstract: Factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is inefficient, complicating mechanistic studies. Here, we examined defined intermediate cell populations poised to becoming iPSCs by genome-wide analyses. W...
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HDAC1-mSin3a-NCOR1, Dnmt3b-HDAC1-Egr1 and Dnmt1-PCNA-UHRF1-G9a regulate the NY-ESO1 gene expression
Published: December, 2012

Abstract: The NY-ESO1 gene is a cancer/testis antigen considered to be suitable target for the immunotherapy of human malignancies. Despite the identification of the epigenetical silencing of the NY-ESO1 gene in a large variety of tumors, the molecular mech...
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Hypoxia-inducible Factor 1α regulates a Socs3-Stat3-adiponectin signal transduction pathway in adipocytes.
Published: December, 2012

Abstract: Obesity has been identified as a major risk factor for type 2 diabetes, characterized by insulin resistance in insulin target tissues. Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity....
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The EP300, KDM5A, KDM6A and KDM6B Chromatin Regulators Cooperate with KLF4 in the Transcriptional Activation of POU5F1.
Published: December, 2012

Abstract: POU5F1 is essential for maintaining pluripotency in embryonic stem cells (ESCs). It has been reported that the constitutive activation of POU5F1 is sustained by the core transcriptional regulatory circuitry in ESCs; however, the means by which POU...
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High-resolution transcriptome and genome-wide dynamics of RNA polymerase and NusA in Mycobacterium tuberculosis.
Published: December, 2012

Abstract: To construct a regulatory map of the genome of the human pathogen, Mycobacterium tuberculosis, we applied two complementary high-resolution approaches: strand-specific RNA-seq, to survey the global transcriptome, and ChIP-seq, to monitor the genom...
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STAT3 Protein Up-regulates Gα-interacting Vesicle-associated Protein (GIV)/Girdin Expression, and GIV Enhances STAT3 Activation in a Positive Feedback Loop during Wound Healing and Tumor Invasion/Metastasis.
Published: December, 2012

Abstract: Gα-interacting vesicle-associated protein (GIV) is a guanine nucleotide exchange factor that modulates key signaling pathways during a diverse set of biological processes, e.g. wound healing, macrophage chemotaxis, tumor angiogenesis, vascular rep...
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A Histone Deacetylase Adjusts Transcription Kinetics at Coding Sequences during Candida albicans Morphogenesis.
Published: December, 2012

Abstract: Despite their classical role as transcriptional repressors, several histone deacetylases, including the baker's yeast Set3/Hos2 complex (Set3C), facilitate gene expression. In the dimorphic human pathogen Candida albicans, the homologue of the Set...
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Conserved boundary elements from the Hox complex of mosquito, Anopheles gambiae.
Published: December, 2012

Abstract: The conservation of hox genes as well as their genomic organization across the phyla suggests that this system of anterior-posterior axis formation arose early during evolution and has come under strong selection pressure. Studies in the split Hox...
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Scmh1 has E3 ubiquitin ligase activity for Geminin and histone H2A and regulates Geminin stability directly or indirectly via transcriptional repression of Hoxa9 and Hoxb4.
Published: December, 2012

Abstract: Polycomb-group (PcG) complex 1 acts as an E3 ubiquitin ligase both for histone H2A to silence transcription and for Geminin to regulate its stability. Scmh1 is a sub-stoichiometric component of PcG complex 1 that provides the complex with an inter...
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ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia.
Published: December, 2012

Abstract: Intratumoral hypoxia is associated with poor prognosis, regardless of the mode of therapy. Cancer cells survive this condition through activating several adaptive signaling pathways, including the integrated stress response (ISR) and autophagy. Ac...
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Ezh2 maintains a key phase of muscle satellite cell expansion but does not regulate terminal differentiation.
Published: November, 2012

Abstract: Tissue generation and repair requires a stepwise process of cell fate restriction to ensure adult stem cells differentiate in a timely and appropriate manner. A crucial role has been implicated for Polycomb-group (PcG) proteins and the H3K27me3 re...
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Cdk11-CyclinL Controls the Assembly of the RNA Polymerase II Mediator Complex.
Published: November, 2012

Abstract: The large Mediator (L-Mediator) is a general coactivator of RNA polymerase II transcription and is formed by the reversible association of the small Mediator (S-Mediator) and the kinase-module-harboring Cdk8. It is not known how the kinase module ...
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CTCF Regulates KSHV Latency Transcription by Nucleosome Displacement and RNA Polymerase Programming.
Published: November, 2012

Abstract: CTCF has been implicated in various aspects of viral and host chromatin organization and transcriptional control. We have previously shown that CTCF binds to a cluster of three sites in the first intron of the Kaposi's Sarcoma-Associated HerpesVir...
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Gene regulation by the lysine demethylase KDM4A in Drosophila.
Published: November, 2012

Abstract: Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic an...
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Post-replicative repair involves separase-dependent removal of the kleisin subunit of cohesin.
Published: November, 2012

Abstract: DNA double-strand break repair is critical for cell viability and involves highly coordinated pathways to restore DNA integrity at the lesion. An early event during homology-dependent repair is resection of the break to generate progressively long...
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Analysis of the peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) cistrome reveals novel co-regulatory role of ATF4.
Published: November, 2012

Abstract: ABSTRACT: BACKGROUND: The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta)-dependent regulation of gene expression...
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Expression of Taurine Transporter (TauT) is Modulated by Heat Shock Factor 1 (HSF1) in Motor Neurons of ALS.
Published: November, 2012

Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive paralysis caused by the degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme Cu/Zn su...
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Identification of p21 (CIP1/WAF1) as a direct target gene of HIC1 (hypermethylated in cancer 1).
Published: November, 2012

Abstract: The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) encodes a transcriptional repressor involved in the regulation of growth control and DNA damage response. We previously demonstrated that p57Kip2; a member of the CIP1/KIP family of CDK ...
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Limitations and possibilities of low cell number ChIP-seq.
Published: November, 2012

Abstract: ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting materi...
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Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity
Published: November, 2012

Abstract: Candida albicans is able to undergo reversible morphological changes between yeast and hyphal forms in response to environmental cues. This morphological plasticity is essential for its pathogenesis. Hyphal development requires two temporally link...
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Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.
Published: November, 2012

Abstract: Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylat...
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HMGA1 Reprograms Somatic Cells into Pluripotent Stem Cells by Inducing Stem Cell Transcriptional Networks.
Published: November, 2012

Abstract: BACKGROUND: Although recent studies have identified genes expressed in human embryonic stem cells (hESCs) that induce pluripotency, the molecular underpinnings of normal stem cell function remain poorly understood. The high mobility group A1 (HMGA...
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GADD45G Functions in Male Sex Determination by Promoting p38 Signaling and Sry Expression.
Published: November, 2012

Abstract: Male sex determination in mammals is induced by Sry, a gene whose regulation is poorly understood. Here we show that mice mutant for the stress-response gene Gadd45g display complete male-to-female sex reversal. Gadd45g and Sry have a strikingly s...
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Altered Binding Site Selection of P53 Transcription Cassettes by Hepatitis B Virus X Protein.
Published: November, 2012

Abstract: The key cellular regulator p53 is a common target of viral oncoproteins. However, the mechanism by which p53 transcription regulation is modulated by Hepatitis B virus X protein (HBx) - a transcription co-factor implicated in hepatitis B virus-ass...
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Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease.
Published: November, 2012

Abstract: Huntingtin (Htt) protein interacts with many transcriptional regulators, with widespread disruption to the transcriptome in Huntington's disease (HD) brought about by altered interactions with the mutant Htt (muHtt) protein. Repressor Element-1 Si...
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Protein Group Modification and Synergy in the SUMO Pathway as Exemplified in DNA Repair.
Published: November, 2012

Abstract: Protein modification by SUMO affects a wide range of protein substrates. Surprisingly, although SUMO pathway mutants display strong phenotypes, the function of individual SUMO modifications is often enigmatic, and SUMOylation-defective mutants com...
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Polycomb Group Proteins Bind an engrailed PRE in Both the "ON" and "OFF" Transcriptional States of engrailed.
Published: November, 2012

Abstract: Polycomb group (PcG) and trithorax Group (trxG) proteins maintain the "OFF" and "ON" transcriptional states of HOX genes and other targets by modulation of chromatin structure. In Drosophila, PcG proteins are bound to DNA fragments called Polycomb...
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Piccolo NuA4 catalyzed acetylation of nucleosomal histones: critical roles of an Esa1 Tudor/chromo barrel loop and an Epl1 Enhancer of Polycomb A (EPcA) basic region.
Published: October, 2012

Abstract: Piccolo NuA4 is an essential yeast histone acetyltransferase (HAT) complex that targets histones H4 and H2A in nucleosome substrates. While Piccolo NuA4's catalytic subunit Esa1 alone is unable to acetylate nucleosomal histones, its accessory subu...
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Regulation of Pluripotency and Self- Renewal of ESCs through Epigenetic- Threshold Modulation and mRNA Pruning.
Published: October, 2012

Abstract: Embryonic stem cell (ESC) pluripotency requires bivalent epigenetic modifications of key developmental genes regulated by various transcription factors and chromatin-modifying enzymes. How these factors coordinate with one another to maintain the ...
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High-resolution detection of DNA binding sites of the global transcriptional regulator GlxR in Corynebacterium glutamicum.
Published: October, 2012

Abstract: The transcriptional regulator GlxR has been characterised as a global hub within the gene-regulatory network of Corynebacterium glutamicum. Chromatin immunoprecipitation with a specific anti-GlxR antibody and subsequent high-throughput sequencing ...
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HIF1α is a central regulator of collagen hydroxylation and secretion under hypoxia during bone development
Published: October, 2012

Abstract: Collagen production is fundamental for the ontogeny and the phylogeny of all multicellular organisms. It depends on hydroxylation of proline residues, a reaction that uses molecular oxygen as a substrate. This dependency is expected to limit colla...
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Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1α,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression.
Published: October, 2012

Abstract: The nuclear hormone 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3) or 1,25D) regulates its target genes via activation of the transcription factor vitamin D receptor (VDR) far more specifically than the chromatin modifier trichostatin A (TsA) via i...
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Distinct requirements for Sin3a in perinatal male gonocytes and differentiating spermatogonia.
Published: October, 2012

Abstract: Chromatin modifier Swi-independent 3a (SIN3A), together with associated histone deacetylases, influences gene expression during development and differentiation through a variety of transcription factors in a cell-specific manner. Sin3a is essentia...
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Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency.
Published: October, 2012

Abstract: How cell fate becomes restricted during somatic cell differentiation is a long lasting question in biology. Epigenetic mechanisms not present in pluripotent cells and acquired during embryonic development are expected to stabilise the differentiat...
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Epigenetic Regulation of Condensin-Mediated Genome Organization during the Cell Cycle and upon DNA Damage through Histone H3 Lysine 56 Acetylation.
Published: October, 2012

Abstract: Complex genome organizations participate in various nuclear processes including transcription, DNA replication, and repair. However, the mechanisms that generate and regulate these functional genome structures remain largely unknown. Here, we desc...
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Nucleolar accumulation of APE1 depends on charged lysine residues that undergo acetylation upon genotoxic stress and modulate its BER activity in cells.
Published: October, 2012

Abstract: Apurinic/apyrimidinic endonuclease 1 (APE1) is the main abasic endonuclease in the base excision repair (BER) pathway of DNA lesions caused by oxidation/alkylation in mammalian cells; within nucleoli it interacts with nucleophosmin and rRNA throug...
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MBD2 and multiple domains of CHD4 are required for transcriptional repression by Mi-2/NuRD complexes.
Published: October, 2012

Abstract: Mi-2/nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complexes are important regulators of chromatin structure and DNA accessibility. We examined requirements for individual domains of chromodomain helicase DNA-binding protein 4 ...
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New partners in regulation of gene expression: the enhancer of trithorax and polycomb corto interacts with methylated ribosomal protein l12 via its chromodomain.
Published: October, 2012

Abstract: Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and ...
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FXR Controls the Tumor Suppressor NDRG2 and FXR Agonists Reduce Liver Tumor Growth and Metastasis in an Orthotopic Mouse Xenograft Model.
Published: October, 2012

Abstract: The farnesoid X receptor (FXR) is expressed predominantly in tissues exposed to high levels of bile acids and controls bile acid and lipid homeostasis. FXR(-/-) mice develop hepatocellular carcinoma (HCC) and show an increased prevalence for intes...
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Adhesion Regulates MAP Kinase/Ternary Complex Factor Exchange to Control a Proliferative Transcriptional Switch.
Published: October, 2012

Abstract: BACKGROUND: The ternary complex factors (TCFs; Elk1, Net, and Sap-1) are growth factor-responsive transcription cofactors of serum response factor (SRF) and are activated by MAP kinase (MAPK) phosphorylation to regulate immediate early gene transc...
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Regulation of delta-aminolevulinic Acid dehydratase by krüppel-like factor 1.
Published: October, 2012

Abstract: Krüppel-like factor 1(KLF1) is a hematopoietic-specific zinc finger transcription factor essential for erythroid gene expression. In concert with the transacting factor GATA1, KLF1 modulates the coordinate expression of the genes encoding the mult...
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A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells.
Published: October, 2012

Abstract: ABSTRACT: BACKGROUND: Glucocorticoids, secreted by the adrenals in response to stress, profoundly affect structure and plasticity of neurons. Glucocorticoid action in neurons is mediated by glucocorticoid receptors (GR) that operate as transcripti...
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ChIP-exo Method for Identifying Genomic Location of DNA-Binding Proteins with Near-Single-Nucleotide Accuracy.
Published: October, 2012

Abstract: This unit describes the ChIP-exo methodology, which combines chromatin immunoprecipitation (ChIP) with lambda exonuclease digestion followed by high-throughput sequencing. ChIP-exo allows identification of a nearly complete set of the binding loca...
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Maize Unstable factor for orange1 Is Required for Maintaining Silencing Associated with Paramutation at the pericarp color1 and booster1 Loci.
Published: October, 2012

Abstract: To understand the molecular mechanisms underlying paramutation, we examined the role of Unstable factor for orange1 (Ufo1) in maintaining paramutation at the maize pericarp color1 (p1) and booster1 (b1) loci. Genetic tests revealed that the Ufo1-1...
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The histone demethylase PHF8 is essential for cytoskeleton dynamics.
Published: October, 2012

Abstract: PHF8 is a histone demethylase associated with X-linked mental retardation. It has been described as a transcriptional co-activator involved in cell cycle progression, but its physiological role is still poorly understood. Here we show that PHF8 co...
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FRUIT, a Scar-Free System for Targeted Chromosomal Mutagenesis, Epitope Tagging, and Promoter Replacement in Escherichia coli and Salmonella enterica
Published: September, 2012

Abstract: Recombineering is a widely-used approach to delete genes, introduce insertions and point mutations, and introduce epitope tags into bacterial chromosomes. Many recombineering methods have been described, for a wide range of bacterial species. Thes...
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Chromatin immunoprecipitation and microarray analysis reveal that TFIIB occupies the SL RNA gene promoter region in Trypanosoma brucei chromosomes
Published: September, 2012

Abstract: RNA polymerase II (RNAP-II) synthesizes the m7G-capped Spliced Leader (SL) RNA and most protein-coding mRNAs in trypanosomes. RNAP-II recruitment to DNA usually requires a set of transcription factors that make sequence-specific contacts near tran...
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Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile.
Published: September, 2012

Abstract: The catabolite control protein CcpA is a pleiotropic regulator that mediates the global transcriptional response to rapidly catabolizable carbohydrates, like glucose in Gram-positive bacteria. By whole transcriptome analyses, we characterized gluc...
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Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage.
Published: September, 2012

Abstract: Heart development is exquisitely sensitive to the precise temporal regulation of thousands of genes that govern developmental decisions during differentiation. However, we currently lack a detailed understanding of how chromatin and gene expressio...
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A GWAS sequence variant for platelet volume marks an alternative DNM3 promoter in megakaryocytes near a MEIS1 binding site.
Published: September, 2012

Abstract: We recently identified 68 genomic loci where common sequence variants are associated with platelet count and volume. Platelets are formed in the bone marrow by megakaryocytes, which are derived from hematopoietic stem cells by a process mainly con...
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A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development.
Published: September, 2012

Abstract: Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Although it is known that chromatin modification patterns in ESCs diffe...
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Expression of MUC17 Is Regulated by HIF1α-Mediated Hypoxic Responses and Requires a Methylation-Free Hypoxia Responsible Element in Pancreatic Cancer.
Published: September, 2012

Abstract: MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinom...
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Argonaute proteins couple chromatin silencing to alternative splicing.
Published: September, 2012

Abstract: Argonaute proteins play a major part in transcriptional gene silencing in many organisms, but their role in the nucleus of somatic mammalian cells remains elusive. Here, we have immunopurified human Argonaute-1 and Argonaute-2 (AGO1 and AGO2) chro...
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A Snapshot of Histone Modifications within Transposable Elements in Drosophila Wild Type Strains.
Published: September, 2012

Abstract: Transposable elements (TEs) are a major source of genetic variability in genomes, creating genetic novelty and driving genome evolution. Analysis of sequenced genomes has revealed considerable diversity in TE families, copy number, and localizatio...
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Multigenerational epigenetic adaptation of the hepatic wound-healing response.
Published: September, 2012

Abstract: We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic ...
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Mutant p53 is a transcriptional co-factor that binds to G-rich regulatory regions of active genes and generates transcriptional plasticity
Published: September, 2012

Abstract: The molecular mechanisms underlying mutant p53 (mutp53) “gain-of-function” (GOF) are still insufficiently understood, but there is evidence that mutp53 is a transcriptional regulator that is recruited by specialized transcription factors. Here we ...
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Genome-Wide Profiling of Peroxisome Proliferator-Activated Receptor γ in Primary Epididymal, Inguinal, and Brown Adipocytes Reveals Depot-Selective Binding Correlated with Gene Expression.
Published: September, 2012

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and function. We and others have previously mapped PPARγ binding at a genome-wide level in murine and human adipocyte cell lines and in primary...
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Widespread plasticity in CTCF occupancy linked to DNA methylation.
Published: September, 2012

Abstract: CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have lon...
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PARP activation regulates the RNA-binding protein NONO in the DNA damage response to DNA double-strand breaks.
Published: August, 2012

Abstract: After the generation of DNA double-strand breaks (DSBs), poly(ADP-ribose) polymerase-1 (PARP-1) is one of the first proteins to be recruited and activated through its binding to the free DNA ends. Upon activation, PARP-1 uses NAD(+) to generate la...
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MutSβ and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells.
Published: August, 2012

Abstract: Trinucleotide repeat (TNR) expansions cause at least 17 heritable neurological diseases, including Huntington's disease. Expansions are thought to arise from abnormal processing of TNR DNA by specific trans-acting proteins. For example, the DNA re...
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Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state.
Published: August, 2012

Abstract: Classical dendritic cells (cDCs) process and present antigens to T cells. Under steady-state conditions, antigen presentation by cDCs induces tolerance. In contrast, during infection or inflammation, cDCs become activated, express higher levels of...
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Genomic Profiling of a Human Organotypic Model of AEC Syndrome Reveals ZNF750 as an Essential Downstream Target of Mutant TP63.
Published: August, 2012

Abstract: The basis for impaired differentiation in TP63 mutant ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome is unknown. Human epidermis harboring AEC TP63 mutants recapitulated this impairment, along with downregulation of differentiation a...
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Nuclear orphan receptor NR2F6 directly antagonizes NFAT and RORγt binding to the Il17a promoter.
Published: August, 2012

Abstract: Interleukin-17A (IL-17A) is the signature cytokine produced by Th17 CD4(+) T cells and has been tightly linked to autoimmune pathogenesis. In particular, the transcription factors NFAT and RORγt are known to activate Il17a transcription, although ...
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Use of allele-specific FAIRE to determine functional regulatory polymorphism using large-scale genotyping arrays.
Published: August, 2012

Abstract: Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify ge...
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The transcription factor Wilms tumor 1 confers resistance in myeloid leukemia cells against the proapoptotic therapeutic agent TRAIL by regulating the antiapoptotic protein Bcl-xL.
Published: August, 2012

Abstract: TRAIL is considered a promising cancer therapeutic agent due to its ability to induce apoptosis in a variety of cancer cells, while sparing normal cells. However, many human tumors including acute myeloid leukemia (AML) are partially or completely...
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Role of the HSP90-Associated Cochaperone p23 in Enhancing Activity of the Androgen Receptor and Significance for Prostate Cancer.
Published: August, 2012

Abstract: Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly u...
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Molecular basis for the specification of floral organs by APETALA3 and PISTILLATA.
Published: August, 2012

Abstract: How different organs are formed from small sets of undifferentiated precursor cells is a key question in developmental biology. To understand the molecular mechanisms underlying organ specification in plants, we studied the function of the homeoti...
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Negative Regulation of Osteoclast Precursor Differentiation by CD11b and beta2 Integrin-BCL6 Signaling
Published: August, 2012

Abstract: Negative regulation of osteoclastogenesis is important for bone homeostasis and prevention of excessive bone resorption in inflammatory and other diseases. Mechanisms that directly suppress osteoclastogenesis are not well understood. In this study...
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KAP1/TRIM28: an inhibitor of IRF5 function in inflammatory macrophages
Published: August, 2012

Abstract: IRF5 plays a key role in the induction of pro-inflammatory cytokines, contributing to the plasticity and polarisation of macrophages to an M1 phenotype and initiation of a potent TH1-TH17 response. To better understand the means of IRF5 transcript...
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IRF-1 and miRNA126 Modulate VCAM-1 Expression in Response to a High Fat Meal.
Published: August, 2012

Abstract: Rationale: A high-fat diet accompanied by hypertriglyceridemia increases an individual's risk for developing atherosclerosis. An early event in this process is monocyte recruitment through binding to VCAM-1 upregulated on inflamed arterial endothe...
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Androgen Receptor Antagonism by Divalent Ethisterone Conjugates in Castrate-Resistant Prostate Cancer Cells.
Published: August, 2012

Abstract: Sustained treatment of prostate cancer with androgen receptor (AR) antagonists can evoke drug resistance, leading to castrate-resistant disease. Elevated activity of the AR is often associated with this highly aggressive disease state. Therefore, ...
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Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia.
Published: August, 2012

Abstract: Glucocorticoids (GCs) are among the most widely prescribed medications in clinical practice. The beneficial effects of GCs in acute lymphoblastic leukemia (ALL) are based on their ability to induce apoptosis, but the underlying transcriptional mec...
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Selective targeting of the repressive transcription factors YY1 and cMyc to disrupt quiescent human immunodeficiency viruses.
Published: August, 2012

Abstract: Quiescent HIV-1 infection of resting CD4+ T cells is an obstacle to eradication of HIV-1 infection. These reservoirs are maintained, in part, by repressive complexes that bind to the HIV-1 long terminal repeat (LTR) and recruit histone deacetylase...
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DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons.
Published: August, 2012

Abstract: The plant-specific DNA-dependent RNA polymerase V (Pol V) evolved from Pol II to function in an RNA-directed DNA methylation pathway. Here, we have identified targets of Pol V in Arabidopsis thaliana on a genome-wide scale using ChIP-seq of NRPE1,...
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Generation of DNA single-strand displacement by compromised nucleotide excision repair.
Published: August, 2012

Abstract: Nucleotide excision repair (NER) is a precisely coordinated process essential to avoid DNA damage-induced cellular malfunction and mutagenesis. Here, we investigate the mechanistic details and effects of the NER machinery when it is compromised by...
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Carm1 Regulates Pax7 Transcriptional Activity through MLL1/2 Recruitment during Asymmetric Satellite Stem Cell Divisions.
Published: August, 2012

Abstract: In skeletal muscle, asymmetrically dividing satellite stem cells give rise to committed satellite cells that transcribe the myogenic determination factor Myf5, a Pax7-target gene. We identified the arginine methyltransferase Carm1 as a Pax7 intera...
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Functional Cooperation between Human Adenovirus Type 5 Early Region 4, Open Reading Frame 6 Protein, and Cellular Homeobox Protein HoxB7.
Published: August, 2012

Abstract: Human adenovirus type 5 (HAdV5) E4orf6 (early region 4 open reading frame 6 protein) is a multifunctional early viral protein promoting efficient replication and progeny production. E4orf6 complexes with E1B-55K to assemble cellular proteins into ...
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Epigenetic Silencing of Cd8 Genes by ThPOK-Mediated Deacetylation during CD4 T Cell Differentiation.
Published: August, 2012

Abstract: Intrathymic CD4/CD8 differentiation is a process that establishes the mutually exclusive expression profiles of the CD4 and CD8 T cell lineage. The RUNX3-mediated silencing of CD4 in CD8 lineage cells has been well documented; however, it is uncle...
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Chromatin Immunoprecipitation Analysis of Xenopus Embryos
Published: August, 2012

Abstract: Chromatin immunoprecipitation (ChIP) is a powerful technique to study epigenetic regulation and transcription factor binding events in the nucleus. It is based on immune-affinity capture of epitopes that have been cross-linked to genomic DNA in vi...
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TMPRSS2- Driven ERG Expression In Vivo Increases Self-Renewal and Maintains Expression in a Castration Resistant Subpopulation.
Published: July, 2012

Abstract: Genomic rearrangements commonly occur in many types of cancers and often initiate or alter the progression of disease. Here we describe an in vivo mouse model that recapitulates the most frequent rearrangement in prostate cancer, the fusion of the...
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Retinoic acid receptors recognize the mouse genome through binding elements with diverse spacing and topology.
Published: July, 2012

Abstract: Retinoic acid receptors (RARs) heterodimerize with retinoid X receptors (RXRs) and bind to RA response elements (RAREs) in the regulatory regions of their target genes. Although previous studies on limited sets of RA-regulated genes have defined c...
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ChAP-MS: A Method for Identification of Proteins and Histone Posttranslational Modifications at a Single Genomic Locus.
Published: July, 2012

Abstract: The field of epigenomics has been transformed by chromatin immunoprecipitation approaches that provide for the localization of a defined protein or posttranslationally modified protein to specific chromosomal sites. While these approaches have hel...
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Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.
Published: July, 2012

Abstract: Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy t...
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Protein kinase CK2 inactivates PRH/Hhex using multiple mechanisms to de-repress VEGF-signalling genes and promote cell survival.
Published: July, 2012

Abstract: Protein kinase CK2 promotes cell survival and the activity of this kinase is elevated in several cancers including chronic myeloid leukaemia. We have shown previously that phosphorylation of the Proline-Rich Homeodomain protein (PRH/Hhex) by CK2 i...
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Curcumin induces human cathelicidin antimicrobial peptide gene expression through a vitamin D receptor-independent pathway.
Published: July, 2012

Abstract: The vitamin D receptor (VDR) mediates the pleiotropic biologic effects of 1α,25 dihydroxy-vitamin D(3). Recent in vitro studies suggested that curcumin and polyunsaturated fatty acids (PUFAs) also bind to VDR with low affinity. As potential ligand...
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Chromatin measurements reveal contributions of synthesis and decay to steady-state mRNA levels.
Published: July, 2012

Abstract: Messenger RNA levels in eukaryotes are controlled by multiple consecutive regulatory processes, which can be classified into two layers: primary transcriptional regulation at the chromosomal level and secondary, co- and post-transcriptional regula...
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A Key Role for Chd1 in Histone H3 Dynamics at the 3′ Ends of Long Genes in Yeast
Published: July, 2012

Abstract: Chd proteins are ATP–dependent chromatin remodeling enzymes implicated in biological functions from transcriptional elongation to control of pluripotency. Previous studies of the Chd1 subclass of these proteins have implicated them in diverse role...
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Genome-wide Analysis Reveals Extensive Functional Interaction between DNA Replication Initiation and Transcription in the Genome of Trypanosoma brucei
Published: July, 2012

Abstract: Identification of replication initiation sites, termed origins, is a crucial step in understanding genome transmission in any organism. Transcription of the Trypanosoma brucei genome is highly unusual, with each chromosome comprising a few discret...
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Ecdysone Induced Gene Expression Is Associated with Acetylation of Histone H3 Lysine 23 in Drosophila melanogaster
Published: July, 2012

Abstract: Posttranslational modification of histones regulates transcription but the exact role that acetylation of specific lysine residues plays in biological processes in vivo is still not clearly understood. To assess the contribution of different histo...
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Glucocorticoids Modulate the mTOR Pathway in the Hippocampus: Differential Effects Depending on Stress History.
Published: July, 2012

Abstract: Glucocorticoid (GC) hormones, released by the adrenals in response to stress, are key regulators of neuronal plasticity. In the brain, the hippocampus is a major target of GC, with abundant expression of the GC receptor. GC differentially affect t...
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The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors.
Published: July, 2012

Abstract: Thymopoiesis depends on the recruitment and expansion of bone marrow-derived progenitor populations; tight regulation of these processes is required for maintenance of the homeostasis of the T lineage. Lyl-1, a transcription factor that regulates ...
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SATB1-mediated Functional Packaging of Chromatin into Loops.
Published: July, 2012

Abstract: Mammalian genomes are organized into multiple layers of higher-order chromatin structure, and in this organization chromatin looping is a striking and crucial feature that brings together distal genomic loci into close spatial proximity. Such thre...
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Histone H2B monoubiquitination is required to reach maximal transcript levels of circadian clock genes in Arabidopsis
Published: July, 2012

Abstract: Previously, we had identified HISTONE MONOUBIQUITINATION1 (HUB1) as an unconventional ubiquitin E3 ligase that was not involved in protein degradation but in histone H2B modification implicated in transcription activation in plants. HUB1-mediated ...
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Lipocalin 2 (LCN2), the TNF-like receptor TWEAKR and its ligand TWEAK act downstream of NFAT1 to regulate breast cancer cell invasion.
Published: July, 2012

Abstract: NFAT1 is a transcription factor that elicits breast carcinoma cells to become invasive, contributing thus to formation of metastasis. The molecular mechanisms by which NFAT1 operates in this respect are still poorly known. Here, we report that NFA...
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The human CST complex is a terminator of telomerase activity.
Published: July, 2012

Abstract: The lengths of human telomeres, which protect chromosome ends from degradation and end fusions, are crucial determinants of cell lifespan. During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in ...
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Aberrant expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice.
Published: July, 2012

Abstract: The Th2 locus control region (LCR) has been shown to be a crucial cis-acting element for Th2 cytokine expression and Th2 cell differentiation. To study the role of Th2 LCR in ifng locus regulation, we examined the expression of IFN-γ in Th2 cells ...
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XPG and XPF Endonucleases Trigger Chromatin Looping and DNA Demethylation for Accurate Expression of Activated Genes.
Published: July, 2012

Abstract: Nucleotide excision repair factors, initially characterized as part of DNA repair, have been shown to participate in the transcriptional process in the absence of genotoxic attack. However, their molecular function when recruited at the promoters ...
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Occludin is a direct target of thyroid transcription factor-1 (TTF-1/NKX2-1).
Published: July, 2012

Abstract: The thyroid transcription factor 1 gene (TTF-1 or NKX2-1) is essential to lung development; however, it is also a critical factor in lung cancer. TTF-1 is amplified in lung cancers, suggesting that it is a gain-of-function lung oncogene. Conversel...
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Genome-wide characterization of Foxa2 targets reveals upregulation of floor plate genes and repression of ventrolateral genes in midbrain dopaminergic progenitors.
Published: July, 2012

Abstract: The transcription factors Foxa1 and Foxa2 promote the specification of midbrain dopaminergic (mDA) neurons and the floor plate. Whether their role is direct has remained unclear as they also regulate the expression of Shh, which has similar roles....
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Quantitative single-molecule microscopy reveals that CENP-A(Cnp1) deposition occurs during G2 in fission yeast.
Published: July, 2012

Abstract: The inheritance of the histone H3 variant CENP-A in nucleosomes at centromeres following DNA replication is mediated by an epigenetic mechanism. To understand the process of epigenetic inheritance, or propagation of histones and histone variants, ...
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Transcription termination between polo and snap, two closely spaced tandem genes of D. melanogaster.
Published: July, 2012

Abstract: Transcription termination of RNA polymerase II between closely spaced genes is an important, though poorly understood, mechanism. This is true, in particular, in the Drosophila genome, where approximately 52% of tandem genes are separated by less ...
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Live cell monitoring of periodic gene expression in synchronous human cells identifies forkhead genes involved in cell cycle control
Published: June, 2012

Abstract: We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S, or a basal promoter with six Forkhead DNA ...
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Cohesins Repress KSHV Immediate Early Gene Transcription During Latency.
Published: June, 2012

Abstract: Chromatin-organizing factors, like CTCF and cohesins, have been implicated in the control of complex viral regulatory programs. We investigated the role of CTCF and cohesin in the control of the latent to lytic switch for Kaposi's Sarcoma-Associat...
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Neurog2 Simultaneously Activates and Represses Alternative Gene Expression Programs in the Developing Neocortex.
Published: June, 2012

Abstract: Progenitor cells undergo a series of stable identity transitions on their way to becoming fully differentiated cells with unique identities. Each cellular transition requires that new sets of genes are expressed, while alternative genetic programs...
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Cdc28 kinase activity regulates the basal transcription machinery at a subset of genes.
Published: June, 2012

Abstract: The cyclin-dependent kinase Cdc28 is the master regulator of the cell cycle in Saccharomyces cerevisiae. Cdc28 initiates the cell cycle by activating cell-cycle-specific transcription factors that switch on a transcriptional program during late G1...
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ZRF1 controls oncogene-induced senescence through the INK4-ARF locus.
Published: June, 2012

Abstract: The reactivation of the INK4-ARF locus, which is epigenetically repressed by Polycomb proteins in healthy cells, is a hallmark of senescence. One mechanism of reactivating Polycomb-silenced genes is mediated by the epigenetic factor ZRF1, which as...
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Histone demethylase Kdm4b functions as a co-factor of C/EBPβ to promote mitotic clonal expansion during differentiation of 3T3-L1 preadipocytes.
Published: June, 2012

Abstract: CCAAT/enhancer-binding protein (C/EBP) β is required for both mitotic clonal expansion (MCE) and terminal adipocyte differentiation of 3T3-L1 preadipocytes. Although the role of C/EBPβ in terminal adipocyte differentiation is well defined, its mec...
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The Saccharomyces cerevisiae Hot1p regulated gene YHR087W (HGI1) has a role in translation upon high glucose concentration stress.
Published: June, 2012

Abstract: ABSTRACT: BACKGROUND: While growing in natural environments yeasts can be affected by osmotic stress provoked by high glucose concentrations. The response to this adverse condition requires the HOG pathway and involves transcriptional and posttran...
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Topoisomerase II is required for the production of long Pol II gene transcripts in yeast.
Published: June, 2012

Abstract: The extent to which the DNA relaxation activities of eukaryotic topoisomerases (topo I and topo II) are redundant during gene transcription is unclear. Although both enzymes can often substitute for each other in vivo, studies in vitro had reveale...
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A Cell Cycle Role for the Epigenetic Factor CTCF-L/BORIS.
Published: June, 2012

Abstract: CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The c...
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The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo.
Published: June, 2012

Abstract: The CACCC-box binding protein Erythroid Krüppel-like Factor (EKLF/KLF1) is a master regulator that directs the expression of many important erythroid genes. We have previously shown that EKLF drives transcription of a second Klf, Basic Krüppel-lik...
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Extensive promoter hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia.
Published: June, 2012

Abstract: Dysregulated microRNA (miRNA) expression contributes to the pathogenesis of hematopoietic malignancies, including chronic lymphocytic leukemia (CLL). However, an understanding of the mechanisms that cause aberrant miRNA transcriptional control is ...
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Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor YY1 in skeletal muscle
Published: June, 2012

Abstract: Formation, distribution and maintenance of functional mitochondria are achieved through dynamic processes that strictly depend on transcription of nuclear genes encoding for mitochondrial proteins. A large number of these mitochondrial genes conta...
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GSK3-SCF(FBXW7) targets JunB for degradation in G2 to preserve chromatid cohesion before anaphase.
Published: June, 2012

Abstract: JunB, an activator protein-1 (AP-1) transcription factor component, acts either as a tumor suppressor or as an oncogene depending on the cell context. In particular, JunB is strongly upregulated in anaplastic lymphoma kinase (ALK)-positive anaplas...
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PGC-1β regulates mouse carnitine-acylcarnitine translocase through estrogen-related receptor α
Published: June, 2012

Abstract: Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficie...
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Phosphorylated and small ubiquitin-like modifier protein-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.
Published: June, 2012

Abstract: ABSTRACT: INTRODUCTION: Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct phosphorylation. PR-B but not PR-A isof...
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Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice.
Published: June, 2012

Abstract: Locally acting insulin growth factor isoform (mIGF-1) and the NAD+-dependent protein deacetylase SIRT1 are implicated in life and health span. Heart failure is associated with aging and is a major cause of death. mIGF-1 protects the heart from oxi...
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Functional characterization of the promoter region of the human EVI1 gene in acute myeloid leukemia: RUNX1 and ELK1 directly regulate its transcription.
Published: June, 2012

Abstract: The EVI1 gene (3q26) codes for a transcription factor with important roles in normal hematopoiesis and leukemogenesis. High expression of EVI1 is a negative prognostic indicator of survival in acute myeloid leukemia (AML) irrespective of the prese...
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RNA Polymerase II Pausing Downstream of Core Histone Genes Is Different from Genes Producing Polyadenylated Transcripts.
Published: June, 2012

Abstract: Recent genome-wide chromatin immunoprecipitation coupled high throughput sequencing (ChIP-seq) analyses performed in various eukaryotic organisms, analysed RNA Polymerase II (Pol II) pausing around the transcription start sites of genes. In this s...
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Transcriptional networks driving enhancer function in the CFTR gene.
Published: June, 2012

Abstract: A critical cis-regulatory element for the cystic fibrosis transmembrane conductance regulator (CFTR) gene is located in intron 11, 100 kb distal to the promoter, with which it interacts. This sequence contains an intestine-selective enhancer and a...
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GSK3 Temporally Regulates Neurogenin 2 Proneural Activity in the Neocortex.
Published: June, 2012

Abstract: The neocortex is comprised of six neuronal layers that are generated in a defined temporal sequence. While extrinsic and intrinsic cues are known to regulate the sequential production of neocortical neurons, how these factors interact and function...
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Developmentally non-redundant SET domain proteins SUVH2 and SUVH9 are required for transcriptional gene silencing in Arabidopsis thaliana.
Published: June, 2012

Abstract: In plants, RNA-directed DNA methylation (RdDM) and related transcriptional gene silencing (TGS) involve members of the suppressor of variegation 3-9-homologous (SUVH) group of putative histone methyltransferases. Utilizing a reverse genetic approa...
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SUMO-targeted ubiquitin E3 ligase RNF4 is required for the response of human cells to DNA damage.
Published: June, 2012

Abstract: Here we demonstrate that RNF4, a highly conserved small ubiquitin-like modifier (SUMO)-targeted ubiquitin E3 ligase, plays a critical role in the response of mammalian cells to DNA damage. Human cells in which RNF4 expression was ablated by siRNA ...
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FOXO1 in the ventromedial hypothalamus regulates energy balance.
Published: June, 2012

Abstract: The transcription factor FOXO1 plays a central role in metabolic homeostasis by regulating leptin and insulin activity in many cell types, including neurons. However, the neurons mediating these effects and the identity of the molecular targets th...
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Histone H2B Ubiquitylation Promotes Activity of the Intact Set1 Histone Methyltransferase Complex in Fission Yeast.
Published: June, 2012

Abstract: The methylation of histone H3 at lysine 4 (H3K4me) is critical for the formation of transcriptionally active chromatin in eukaryotes. In yeast, Drosophila, and some human cell lines, H3K4me is globally stimulated by the monoubiquitylation of histo...
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Preferential Genome Targeting of the CBP Co-Activator by Rel and Smad Proteins in Early Drosophila melanogaster Embryos.
Published: June, 2012

Abstract: CBP and the related p300 protein are widely used transcriptional co-activators in metazoans that interact with multiple transcription factors. Whether CBP/p300 occupies the genome equally with all factors or preferentially binds together with some...
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Multiple Histone Methyl and Acetyltransferase Complex Components Bind the HLA-DRA Gene.
Published: May, 2012

Abstract: Major histocompatibility complex class II (MHC-II) genes are fundamental components that contribute to adaptive immune responses. While characterization of the chromatin features at the core promoter region of these genes has been studied, the sco...
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Serum Response Factor and cAMP Response Element Binding Protein Are Both Required for Cocaine Induction of {Delta}FosB.
Published: May, 2012

Abstract: The molecular mechanism underlying induction by cocaine of ΔFosB, a transcription factor important for addiction, remains unknown. Here, we demonstrate a necessary role for two transcription factors, cAMP response element binding protein (CREB) an...
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Genome-Wide Characterization of Menin-Dependent H3K4me3 Reveals a Specific Role for Menin in the Regulation of Genes Implicated in MEN1-Like Tumors.
Published: May, 2012

Abstract: Inactivating mutations in the MEN1 gene predisposing to the multiple endocrine neoplasia type 1 (MEN1) syndrome can also cause sporadic pancreatic endocrine tumors. MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone methyltransferase co...
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Mus81-Mms4 function as a single heterodimer to cleave nicked intermediates in recombinational DNA repair.
Published: May, 2012

Abstract: The formation of crossovers is a fundamental genetic process. The XPF-family endonuclease, Mus81-Mms4 (Eme1), contributes significantly to crossing-over in eukaryotes. A key question is whether Mus81-Mms4 can process Holliday junctions that contai...
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The aryl hydrocarbon receptor ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene regulate distinct genetic networks.
Published: May, 2012

Abstract: The two estrogen receptor isoforms ERα and ERβ mediate biological effects of estrogens, but are also targets for endocrine disruptive chemicals (EDCs), compounds that interfere with hormonal signaling. 3-Methylcholanthrene (3-MC) and dioxin (TCDD)...
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Functional Genomic Methods to Study Estrogen Receptor Activity.
Published: May, 2012

Abstract: Estrogen Receptor (ER) is a nuclear receptor that mediates the actions of estrogen and tamoxifen. ER is expressed in a major fraction of human breast cancers. Recently, genomic maps for estrogen- and tamoxifen-ER have been published. Interestingly...
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Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis.
Published: May, 2012

Abstract: The generation of distinctive cell types that form different tissues and organs requires precise, temporal and spatial control of gene expression. This depends on specific cis-regulatory elements distributed in the non-coding DNA surrounding their...
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The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3.
Published: May, 2012

Abstract: Lineage commitment studies in mammary glands have focused on identifying cell populations that display stem or progenitor properties. However, the mechanisms that control cell fate have been incompletely explored. Herein we show that zinc finger p...
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The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells.
Published: May, 2012

Abstract: Histone deacetylases (HDACs) are a family of 18 enzymes that deacetylate lysine residues of both histone and nonhistone proteins and to a large extent govern the process of angiogenesis. Previous studies have shown that specific inhibition of HDAC...
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HIF1A induces expression of the WASF3 metastasis-associated gene under hypoxic conditions.
Published: May, 2012

Abstract: The WASF3 (WAVE3) gene is an important mediator of cell motility, invasion and metastasis and is expressed at high levels in some advanced stage tumors. In our survey of breast cancer cells, we now demonstrate that exposure to hypoxic conditions i...
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The linker histone plays a dual role during gametogenesis in S. cerevisiae.
Published: May, 2012

Abstract: The differentiation of gametes involves dramatic changes to chromatin, affecting transcription, meiosis, and cell morphology. Sporulation in S. cerevisiae shares many chromatin features with spermatogenesis, including a ten-fold compaction of the ...
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BIM promoter directly targeted by EBNA3C in polycomb-mediated repression by EBV.
Published: May, 2012

Abstract: Detailed analyses of the chromatin around the BIM promoter has revealed that latent Epstein-Barr virus (EBV) triggers the recruitment of polycomb repressive complex 2 (PRC2) core subunits and the trimethylation of histone H3 lysine 27 (H3K27me3) a...
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Glucose-Dependent Regulation of NR2F2 Promoter and Influence of SNP-rs3743462 on Whole Body Insulin Sensitivity.
Published: May, 2012

Abstract: BACKGROUND: The Nuclear Receptor 2F2 (NR2F2/COUP-TFII) heterozygous knockout mice display low basal insulinemia and enhanced insulin sensitivity. We previously established that insulin represses NR2F2 gene expression in pancreatic β-cells. The cis...
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Integrative genomics identifies the corepressor SMRT as a gatekeeper of adipogenesis through the transcription factors C/EBPβ and KAISO.
Published: May, 2012

Abstract: The molecular role of corepressors is poorly understood. Here, we studied the transcriptional function of the corepressor SMRT during terminal adipogenesis. Genome-wide DNA-binding profiling revealed that this corepressor is predominantly located ...
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A Long ncRNA Links Copy Number Variation to a Polycomb/Trithorax Epigenetic Switch in FSHD Muscular Dystrophy.
Published: May, 2012

Abstract: Repetitive sequences account for more than 50% of the human genome. Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease associated with reduction in the copy number of the D4Z4 repeat mapping to 4q35. By an unknown mecha...
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The histone demethylase Kdm3a is essential to progression through differentiation.
Published: May, 2012

Abstract: Histone demethylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity by still poorly understood mechanisms. Here, we examined the role of histone demethylase K...
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Hsp90 globally targets paused RNA polymerase to regulate gene expression in response to environmental stimuli.
Published: May, 2012

Abstract: The molecular chaperone Heat shock protein 90 (Hsp90) promotes the maturation of several important proteins and plays a key role in development, cancer progression, and evolutionary diversification. By mapping chromatin-binding sites of Hsp90 at h...
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Genome-wide analysis of p63 binding sites identifies AP-2 factors as co-regulators of epidermal differentiation.
Published: May, 2012

Abstract: The p63 transcription factor (TP63) is critical in development, growth and differentiation of stratifying epithelia. This is highlighted by the severity of congenital abnormalities caused by TP63 mutations in humans, the dramatic phenotypes in kno...
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RBE controls microRNA164 expression to effect floral organogenesis.
Published: May, 2012

Abstract: The establishment and maintenance of organ boundaries are vital for animal and plant development. In the Arabidopsis flower, three microRNA164 genes (MIR164a, b and c) regulate the expression of CUP-SHAPED COTYLEDON1 (CUC1) and CUC2, which encode ...
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Differential Modulation of the Oligodendrocyte Transcriptome by Sonic Hedgehog and Bone Morphogenetic Protein 4 via Opposing Effects on Histone Acetylation.
Published: May, 2012

Abstract: Differentiation of oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes is regulated by the interplay between extrinsic signals and intrinsic epigenetic determinants. In this study, we analyze the effect that the extracellular liga...
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The Flk1-cre Mediated Deletion of ETV2 Defines Its Narrow Temporal Requirement During Embryonic Hematopoietic Development.
Published: May, 2012

Abstract: During embryonic development, the emergence of hematopoiesis and vasculogenesis is tightly associated, with many transcription factors implicated in both developmental processes. Among those factors, ETV2 acts at the top of the hierarchy and contr...
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High throughput automated chromatin immunoprecipitation as a platform for drug screening and antibody validation.
Published: May, 2012

Abstract: Chromatin immunoprecipitation (ChIP) is an assay for interrogating protein-DNA interactions that is increasingly being used for drug target discovery and screening applications. Currently the complexity of the protocol and the amount of hands-on t...
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Genome-wide search reveals the existence of a limited number of thyroid hormone receptor alpha target genes in cerebellar neurons.
Published: May, 2012

Abstract: Thyroid hormone (T3) has a major influence on cerebellum post-natal development. The major phenotypic landmark of exposure to low levels of T3 during development (hypothyroidism) in the cerebellum is the retarded inward migration of the most numer...
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piRNA-mediated transgenerational inheritance of an acquired trait.
Published: May, 2012

Abstract: The maintenance of genome integrity is an essential trait to the successful transmission of genetic information. In animal germ cells, piRNAs guide PIWI proteins to silence transposable elements (TEs) in order to maintain genome integrity. In inse...
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Psip1/Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing.
Published: May, 2012

Abstract: Increasing evidence suggests that chromatin modifications have important roles in modulating constitutive or alternative splicing. Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically recognize ...
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SOX7 regulates the expression of VE-cadherin in the haemogenic endothelium at the onset of haematopoietic development.
Published: May, 2012

Abstract: At early stages of vertebrate ontogeny, blood and endothelial cells develop from a common mesodermal progenitor, the haemangioblast. Upon haematopoietic commitment, the haemangioblast generates blood precursors through populations of endothelial c...
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Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming.
Published: May, 2012

Abstract: Transcription-factor-directed reprogramming from somatic cells to induced pluripotent stem cells (iPSCs) is by nature an epigenetic process of cell fate change. Previous studies have demonstrated that this inefficient process can be facilitated by...
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Cell type-specific chromatin immunoprecipitation from multicellular complex samples using BiTS-ChIP.
Published: May, 2012

Abstract: This protocol describes the batch isolation of tissue-specific chromatin for immunoprecipitation (BiTS-ChIP) for analysis of histone modifications, transcription factor binding, or polymerase occupancy within the context of a multicellular organis...
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LINT, a Novel dL(3)mbt-Containing Complex, Represses Malignant Brain Tumour Signature Genes.
Published: May, 2012

Abstract: Mutations in the l(3)mbt tumour suppressor result in overproliferation of Drosophila larval brains. Recently, the derepression of different gene classes in l(3)mbt mutants was shown to be causal for transformation. However, the molecular mechanism...
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Dynamic deposition of histone variant h3.3 accompanies developmental remodeling of the Arabidopsis transcriptome.
Published: May, 2012

Abstract: In animals, replication-coupled histone H3.1 can be distinguished from replication-independent histone H3.3. H3.3 variants are enriched at active genes and their promoters. Furthermore, H3.3 is specifically incorporated upon gene activation. Histo...
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Transient neonatal diabetes mellitus gene Zac1 impairs insulin secretion in mice through Rasgrf1.
Published: April, 2012

Abstract: Biallelic expression of the imprinted gene ZAC1/PLAGL1 underlies ∼60% of all cases of transient neonatal diabetes mellitus (TNDM) which present with low perinatal insulin secretion. Molecular targets of ZAC1 misexpression in pancreatic β-cells are...
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The SEC family of RNA Polymerase II elongation factors: gene target specificity and transcriptional output.
Published: April, 2012

Abstract: The elongation stage of transcription is highly regulated in metazoans. We previously purified the AFF1/AFF4-containing Super Elongation Complex (SEC) as a major regulator of development and cancer pathogenesis. Here, we report the biochemical iso...
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iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes.
Published: April, 2012

Abstract: The ability to induce apoptosis is the most important tumor-suppression function of p53. Inhibitory member of apoptosis-stimulating protein of p53 family (iASPP) is an apoptotic-specific regulator of p53. iASPP suppresses apoptosis by inhibiting t...
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Bloom's Syndrome and PICH Helicases Cooperate with Topoisomerase IIα in Centromere Disjunction before Anaphase.
Published: April, 2012

Abstract: Centromeres are specialized chromosome domains that control chromosome segregation during mitosis, but little is known about the mechanisms underlying the maintenance of their integrity. Centromeric ultrafine anaphase bridges are physiological DNA...
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Dendritic Cells Activated by IFN-γ/STAT1 Express IL-31 Receptor and Release Proinflammatory Mediators upon IL-31 Treatment.
Published: April, 2012

Abstract: IL-31 is a T cell-derived cytokine that signals via a heterodimeric receptor composed of IL-31Rα and oncostatin M receptor β. Although several studies have aimed to investigate IL-31-mediated effects, the biological functions of this cytokine are ...
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Uncovering cis-regulatory sequence requirements for context specific transcription factor binding.
Published: April, 2012

Abstract: The regulation of gene expression is mediated at the transcriptional level by enhancer regions that are bound by sequence specific transcription factors (TFs). Recent studies have shown that the in vivo binding sites of single TFs differ between d...
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Genome Wide Analysis Of Pax8 Binding Provides New Insights Into Thyroid Functions.
Published: April, 2012

Abstract: ABSTRACT: BACKGROUND: The transcription factor Pax8 is essential for the differentiation of thyroid cells. However, there are few data on genes transcriptionally regulated by Pax8 other than thyroid-related genes. To better understand the role of ...
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Global analysis of the regulon of the transcriptional repressor LexA, a key component of the SOS response in Mycobacterium tuberculosis.
Published: April, 2012

Abstract: The DNA damage response is crucial for bacterial survival. The transcriptional repressor LexA is a key component of the SOS response, the main mechanism for the regulation of DNA repair genes in many bacteria. In contrast, in mycobacteria gene ind...
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Preparation and use of Xenopus egg extracts to study DNA replication and chromatin associated proteins.
Published: April, 2012

Abstract: The use of cell-free extracts prepared from eggs of the South African clawed toad, Xenopus laevis, has led to many important discoveries in cell cycle research. These egg extracts recapitulate the key nuclear transitions of the eukaryotic cell cyc...
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Developmental silencing of the AtTERT gene is associated with increased H3K27me3 loading and maintenance of its euchromatic environment.
Published: April, 2012

Abstract: Telomerase, an enzyme responsible for the maintenance of linear chromosome ends, is precisely regulated during plant development. In animals, involvement of the epigenetic state of the telomerase reverse transcriptase (TERT) gene in the complex re...
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A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation.
Published: April, 2012

Abstract: The linker histone H1 is a key player in chromatin organization, yet our understanding of the regulation of H1 functions by post-translational modifications is very limited. We provide here the first functional characterization of H1 acetylation. ...
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HDAC1 Regulates Fear Extinction in Mice.
Published: April, 2012

Abstract: Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, litt...
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Miz1 Is a Critical Repressor of cdkn1a during Skin Tumorigenesis.
Published: April, 2012

Abstract: The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15(Ink4)), cdkn1a (p21(Cip1)), and...
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Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation.
Published: April, 2012

Abstract: The ability of skeletal muscle to enhance lipid utilization during exercise is a form of metabolic plasticity essential for survival. Conversely, metabolic inflexibility in muscle can cause organ dysfunction and disease. Although the transcription...
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Yin Yang 1 Deficiency in Skeletal Muscle Protects against Rapamycin-Induced Diabetic-like Symptoms through Activation of Insulin/IGF Signaling.
Published: April, 2012

Abstract: Rapamycin and its derivatives are mTOR inhibitors used in tissue transplantation and cancer therapy. A percentage of patients treated with these inhibitors develop diabetic-like symptoms, but the molecular mechanisms are unknown. We show here that...
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The RNA-Binding Protein Human Antigen R Controls Global Changes in Gene Expression during Schwann Cell Development.
Published: April, 2012

Abstract: An important prerequisite to myelination in peripheral nerves is the establishment of one-to-one relationships between axons and Schwann cells. This patterning event depends on immature Schwann cell proliferation, apoptosis, and morphogenesis, whi...
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A hindbrain-repressive Wnt3a/Meis3/Tsh1 circuit promotes neuronal differentiation and coordinates tissue maturation.
Published: April, 2012

Abstract: During development, early inducing programs must later be counterbalanced for coordinated tissue maturation. In Xenopus laevis embryos, activation of the Meis3 transcription factor by a mesodermal Wnt3a signal lies at the core of the hindbrain dev...
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Rev-erbα and Rev-erbβ coordinately protect the circadian clock and normal metabolic function.
Published: April, 2012

Abstract: The nuclear receptor Rev-erbα regulates circadian rhythm and metabolism, but its effects are modest and it has been considered to be a secondary regulator of the cell-autonomous clock. Here we report that depletion of Rev-erbα together with closel...
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UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair.
Published: April, 2012

Abstract: Transcription-coupled nucleotide-excision repair (TC-NER) is a subpathway of NER that efficiently removes the highly toxic RNA polymerase II blocking lesions in DNA. Defective TC-NER gives rise to the human disorders Cockayne syndrome and UV-sensi...
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A GATA Transcription Factor Recruits Hda1 in Response to Reduced Tor1 Signaling to Establish a Hyphal Chromatin State in Candida albicans.
Published: April, 2012

Abstract: Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. One critical virulence attribute is its morphogenetic plasticity. Hyphal development requires two temporally linked changes in promoter chromatin, whi...
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Frequent aberrant expression of the human ether à go-go (hEAG1) potassium channel in head and neck cancer: pathobiological mechanisms and clinical implications.
Published: March, 2012

Abstract: Compelling evidence indicates that the human ether-à-go-go voltage-gated potassium channels (hEAG1) may represent new valuable membrane therapeutic targets and diagnostic/prognostic biomarkers in various cancers. This study is the first to investi...
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ErbB2-Driven Breast Cancer Cell Invasion Depends on a Complex Signaling Network Activating Myeloid Zinc Finger-1-Dependent Cathepsin B Expression.
Published: March, 2012

Abstract: Aberrant ErbB2 receptor tyrosine kinase activation in breast cancer is strongly linked to an invasive disease. The molecular basis of ErbB2-driven invasion is largely unknown. We show that cysteine cathepsins B and L are elevated in ErbB2 positive...
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Sequential ChIP-bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk.
Published: March, 2012

Abstract: Cross-talk between DNA methylation and histone modifications drives the establishment of composite epigenetic signatures and is traditionally studied using correlative rather than direct approaches. Here we present sequential ChIP-bisulfite-sequen...
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The lhx2 transcription factor controls thalamocortical axonal guidance by specific regulation of robo1 and robo2 receptors.
Published: March, 2012

Abstract: The assembly of neural circuits is dependent upon the generation of specific neuronal subtypes, each subtype displaying unique properties that direct the formation of selective connections with appropriate target cells. Actions of transcription fa...
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Inflammasome-Activated Caspase 7 Cleaves PARP1 to Enhance the Expression of a Subset of NF-κB Target Genes.
Published: March, 2012

Abstract: Caspase 1 is part of the inflammasome, which is assembled upon pathogen recognition, while caspases 3 and/or 7 are mediators of apoptotic and nonapoptotic functions. PARP1 cleavage is a hallmark of apoptosis yet not essential, suggesting it has an...
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Analysis of Chromatin Dynamics during Glucocorticoid Receptor Activation.
Published: March, 2012

Abstract: Steroid hormone receptors initiate a genetic program tightly regulated by the chromatin environment of the responsive regions. Using the glucocorticoid receptor (GR) as a model factor for transcriptional initiation, we classified chromatin structu...
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A dual Role for the dREAM/MMB complex in the regulation of differentiation-specific E2F/RB target genes.
Published: March, 2012

Abstract: E2F and RB proteins regulate the expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. Recent studies indicate that they function as part of an evolutionary conserved multi-protein complex, termed dRE...
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Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics.
Published: March, 2012

Abstract: Synovial sarcoma is a translocation-associated sarcoma where the underlying chromosomal event generates SS18-SSX fusion transcripts. In vitro and in vivo studies have shown that the SS18-SSX fusion oncoprotein is both necessary and sufficient to s...
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Genome-wide analysis of histone H3.1 and H3.3 variants in Arabidopsis thaliana.
Published: March, 2012

Abstract: Nucleosomes package eukaryotic DNA and are composed of four different histone proteins, designated H3, H4, H2A, and H2B. Histone H3 has two main variants, H3.1 and H3.3, which show different genomic localization patterns in animals. We profiled H3...
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DLK2 is a transcriptional target of KLF4 in the early stages of adipogenesis.
Published: March, 2012

Abstract: The epidermal growth factor-like protein DLK2, highly homologous to DLK1, has been identified as a modulator of adipogenesis in vitro. Knocking down Dlk2 expression prevents adipogenesis of 3T3-L1 cells but enhances that of the mesenchymal cell li...
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Identification and characterization of ToRC, a novel ISWI-containing ATP-dependent chromatin assembly complex.
Published: March, 2012

Abstract: SNF2-like motor proteins, such as ISWI, cooperate with histone chaperones in the assembly and remodeling of chromatin. Here we describe a novel, evolutionarily conserved, ISWI-containing complex termed ToRC (Toutatis-containing chromatin remodelin...
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Genome-wide evaluation of histone methylation changes associated with leaf senescence in Arabidopsis.
Published: March, 2012

Abstract: Leaf senescence is the orderly dismantling of older tissue that allows recycling of nutrients to developing portions of the plant and is accompanied by major changes in gene expression. Histone modifications correlate to levels of gene expression,...
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Resveratrol Inhibits KSHV Reactivation by Lowering the Levels of Cellular EGR-1.
Published: March, 2012

Abstract: In the field of herpesvirus research, the exact molecular mechanism by which such viruses reactivate from latency remains elusive. Kaposi's sarcoma-associated herpesvirus (KSHV) primarily exists in a latent state, while only 1-3% of cells support ...
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CBX4-mediated SUMO modification regulates BMI1 recruitment at sites of DNA damage.
Published: March, 2012

Abstract: Polycomb group (PcG) proteins are involved in epigenetic silencing where they function as major determinants of cell identity, stem cell pluripotency and the epigenetic gene silencing involved in cancer development. Recently numerous PcG proteins,...
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Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Published: March, 2012

Abstract: Epigenetic regulation of gene expression is commonly altered in human cancer. We have observed alterations of DNA methylation and microRNA expression that reflect the biology of bladder cancer. This common disease arises by distinct pathways with ...
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Chromatin-modifying enzymes as modulators of reprogramming.
Published: March, 2012

Abstract: Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling. Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells befor...
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Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.
Published: March, 2012

Abstract: The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster, compromising the ability to generate entirely iPSC-derived adult mice ('all-iPSC mice'). Here, we show...
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Mapping and Functional Characterisation of a CTCF-Dependent Insulator Element at the 3' Border of the Murine Scl Transcriptional Domain.
Published: March, 2012

Abstract: The Scl gene encodes a transcription factor essential for haematopoietic development. Scl transcription is regulated by a panel of cis-elements spread over 55 kb with the most distal 3' element being located downstream of the neighbouring gene Map...
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RYBP Represses Endogenous Retroviruses and Preimplantation- and Germ Line-Specific Genes in Mouse Embryonic Stem Cells.
Published: March, 2012

Abstract: Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B and has been suggested to assist PRC localization to their targets. Moreo...
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Pdgfrα and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells.
Published: March, 2012

Abstract: The Mixl1 homeodomain protein plays a key role in mesendoderm patterning during embryogenesis, but its target genes remain to be identified. We compared gene expression in differentiating heterozygous Mixl1(GFP/w) and homozygous null Mixl1(GFP/Hyg...
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The rs3743205 SNP Is Important for the Regulation of the Dyslexia Candidate Gene DYX1C1 by Estrogen Receptor β and DNA Methylation.
Published: March, 2012

Abstract: Estrogen is involved in numerous physiological processes such as growth, differentiation, and function of the male and female reproductive tissues. In the developing brain, estrogen signaling has been linked to cognitive functions, such as learnin...
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EZH2 couples pancreatic regeneration to neoplastic progression.
Published: March, 2012

Abstract: Although the polycomb group protein Enhancer of Zeste Homolog 2 (EZH2) is well recognized for its role as a key regulator of cell differentiation, its involvement in tissue regeneration is largely unknown. Here we show that EZH2 is up-regulated fo...
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Widespread site-dependent buffering of human regulatory polymorphism.
Published: March, 2012

Abstract: The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within a...
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Small-molecule-induced DNA damage identifies alternative DNA structures in human genes.
Published: March, 2012

Abstract: Guanine-rich DNA sequences that can adopt non-Watson-Crick structures in vitro are prevalent in the human genome. Whether such structures normally exist in mammalian cells has, however, been the subject of active research for decades. Here we show...
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RNA Profiling and Chromatin Immunoprecipitation-Sequencing Reveal that PTF1a Stabilizes Pancreas Progenitor Identity via the Control of MNX1/HLXB9 and a Network of Other Transcription Factors.
Published: March, 2012

Abstract: Pancreas development is initiated by the specification and expansion of a small group of endodermal cells. Several transcription factors are crucial for progenitor maintenance and expansion, but their interactions and the downstream targets mediat...
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Dynamic MicroRNA Gene Transcription and Processing during T Cell Development.
Published: February, 2012

Abstract: By disrupting microRNA (miRNA) biogenesis, we previously showed that this pathway is critical for the differentiation and function of T cells. Although various cloning studies have shown that many miRNAs are expressed during T cell development, an...
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Transcriptional induction of salt-inducible kinase 1 by transforming growth factor β leads to negative regulation of type I receptor signaling in cooperation with the Smurf2 ubiquitin ligase.
Published: February, 2012

Abstract: Transforming growth factor β (TGFβ)1 regulates many physiological processes and requires control mechanisms to safeguard proper and timely action. We have previously described how negative regulation of TGFβ signaling is controlled by the serine/t...
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Human Histone Acetyltransferase 1 Protein Preferentially Acetylates H4 Histone Molecules in H3.1-H4 over H3.3-H4.
Published: February, 2012

Abstract: In mammalian cells, canonical histone H3 (H3.1) and H3 variant (H3.3) differ by five amino acids and are assembled, along with histone H4, into nucleosomes via distinct nucleosome assembly pathways. H3.1-H4 molecules are assembled by histone chape...
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Transcriptional Activation of the Adenoviral Genome Is Mediated by Capsid Protein VI
Published: February, 2012

Abstract: Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral d...
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3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a) – A New Tool Used for Identification of Common and Isoform Specific Target Genes
Published: February, 2012

Abstract: Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid inse...
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Dual-Mode Modulation of Smad Signaling by Smad-Interacting Protein Sip1 Is Required for Myelination in the Central Nervous System
Published: February, 2012

Abstract: Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 a...
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Circadian rhythms govern cardiac repolarization and arrhythmogenesis
Published: February, 2012

Abstract: Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease1,2, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnorma...
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Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Published: February, 2012

Abstract: Jarid2 was recently identified as an important component of the mammalian Polycomb Repressive Complex 2 (PRC2), where it has a major effect on PRC2 recruitment in mouse embryonic stem cells. Although Jarid2 is conserved in Drosophila, it has not p...
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The Receptor Tyrosine Kinase EphA2 Is a Direct Target Gene of Hypermethylated in Cancer 1 (HIC1).
Published: February, 2012

Abstract: The tumor suppressor gene hypermethylated in cancer 1 (HIC1), which encodes a transcriptional repressor, is epigenetically silenced in many human tumors. Here, we show that ectopic expression of HIC1 in the highly malignant MDA-MB-231 breast cance...
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The transcription factor Erg controls endothelial cell quiescence by repressing the activity of nuclear factor (NF)-κB p65.
Published: February, 2012

Abstract: The interaction of transcription factors with specific DNA sequences is critical for activation of gene expression programmes. In endothelial cells (EC), the transcription factor NFκB is important in the switch from quiescence to activation, and i...
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Opposing Functions of the ETS Factor Family Define Shh Spatial Expression in Limb Buds and Underlie Polydactyly
Published: February, 2012

Abstract: Sonic hedgehog (Shh) expression during limb development is crucial for specifying the identity and number of digits. The spatial pattern of Shh expression is restricted to a region called the zone of polarizing activity (ZPA), and this expression ...
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Anticheckpoint pathways at telomeres in yeast
Published: February, 2012

Abstract: Telomeres hide (or ‘cap’) chromosome ends from DNA-damage surveillance mechanisms that arrest the cell cycle and promote repair, but the checkpoint status of telomeres is not well understood. Here we characterize the response in Saccharomyces cere...
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A workflow for genome-wide mapping of archaeal transcription factors with ChIP-seq.
Published: February, 2012

Abstract: Deciphering the structure of gene regulatory networks across the tree of life remains one of the major challenges in postgenomic biology. We present a novel ChIP-seq workflow for the archaea using the model organism Halobacterium salinarum sp. NRC...
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Research Resource: The Pdx1 Cistrome of Pancreatic Islets.
Published: February, 2012

Abstract: The homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mu...
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RYBP-PRC1 Complexes Mediate H2A Ubiquitylation at Polycomb Target Sites Independently of PRC2 and H3K27me3.
Published: February, 2012

Abstract: Polycomb-repressive complex 1 (PRC1) has a central role in the regulation of heritable gene silencing during differentiation and development. PRC1 recruitment is generally attributed to interaction of the chromodomain of the core protein Polycomb ...
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Dataset integration identifies transcriptional regulation of microRNA genes by PPARγ in differentiating mouse 3T3-L1 adipocytes.
Published: February, 2012

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a key transcription factor in mammalian adipogenesis. Genome-wide approaches have identified thousands of PPARγ binding sites in mouse adipocytes and PPARγ upregulates hundreds of protein-cod...
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Hypermethylated in cancer 1 (HIC1) recruits polycomb repressive complex 2 (PRC2) to a subset of its target genes through interaction with human polycomb-like (hPCL) proteins.
Published: February, 2012

Abstract: HIC1 (Hypermethylated in Cancer 1) is a tumor suppressor gene epigenetically silenced or deleted in many human cancers. HIC1 is involved in regulatory loops modulating p53- and E2F1-dependent cell survival, growth control and stress responses. HIC...
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The composition and signaling of the IL-35 receptor are unconventional.
Published: February, 2012

Abstract: Interleukin 35 (IL-35) belongs to the IL-12 family of heterodimeric cytokines but has a distinct functional profile. IL-35 suppresses T cell proliferation and converts naive T cells into IL-35-producing induced regulatory T cells (iTr35 cells). He...
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Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation?
Published: February, 2012

Abstract: BACKGROUND: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen rece...
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Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation.
Published: February, 2012

Abstract: Acetyltransferase complexes of the MYST family with distinct substrate specificities and functions maintain a conserved association with different ING tumor suppressor proteins. ING complexes containing the HBO1 acetylase are a major source of his...
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Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development.
Published: February, 2012

Abstract: Chromatin modifications are associated with many aspects of gene expression, yet their role in cellular transitions during development remains elusive. Here, we use a new approach to obtain cell type-specific information on chromatin state and RNA...
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Epigenetic regulation of the latency-associated region of Marek's disease virus in tumor-derived T-cell lines and primary lymphoma.
Published: February, 2012

Abstract: Meq is the major Marek's disease virus (MDV)-encoded oncoprotein and is essential for T-cell lymphomagenesis. Meq and several noncoding RNAs, including three microRNA (MiR) clusters, are expressed from the repeats of the MDV genome during latent i...
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Histone deacetylase 6 (HDAC6) is an essential modifier of glucocorticoid-induced hepatic gluconeogenesis.
Published: February, 2012

Abstract: In the current study, we investigated the importance of histone deacetylase (HDAC)6 for glucocorticoid receptor-mediated effects on glucose metabolism and its potential as a therapeutic target for the prevention of glucocorticoid-induced diabetes....
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Genome-wide landscape of liver X receptor chromatin binding and gene regulation in human macrophages.
Published: January, 2012

Abstract: ABSTRACT: BACKGROUND: The liver X receptors (LXRs) are oxysterol sensing nuclear receptors with multiple effects on metabolism and immune cells. However, the complete genome-wide cistrome of LXR in cells of human origin has not yet been provided. ...
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The Spt5 C-terminal region recruits yeast 3’-RNA cleavage factor I
Published: January, 2012

Abstract: During transcription elongation, RNA polymerase (Pol) II binds the general elongation factor Spt5. Spt5 contains a repetitive C-terminal region (CTR) that is required for co-transcriptional recruitment of the Paf1 complex (44, 88). Here we report ...
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Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin.
Published: January, 2012

Abstract: Although stress can suppress growth and proliferation, cells can induce adaptive responses that allow them to maintain these functions under stress. While numerous studies have focused on the inhibitory effects of stress on cell growth, less is kn...
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Histone deacetylase 1 is required for Carbamazepine-induced CYP3A4 expression.
Published: January, 2012

Abstract: Carbamazepine (CBZ) is a commonly prescribed antiepileptic drug. Adverse effects and drug-drug interaction are the two major concerns for its clinic application. CBZ is mainly metabolized by cytochrome P450 (CYP) 3A4, a strong inducer of CYP3A4 as...
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Histone deacetylase inhibitors sensitize glioblastoma cells to TRAIL-induced apoptosis by c-myc-mediated downregulation of cFLIP.
Published: January, 2012

Abstract: Glioblastoma is the most common primary brain tumor with a very poor prognosis, calling for novel treatment strategies. Here, we provide first evidence that histone deacetylase inhibitors (HDACI) prime glioblastoma cells for tumor necrosis factor-...
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Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor.
Published: January, 2012

Abstract: Ddx5 and ddx17 are two highly related RNA helicases involved in both transcription and splicing. These proteins coactivate transcription factors involved in cancer such as the estrogen receptor alpha, p53 and beta-catenin. Ddx5 and ddx17 are part ...
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A novel retinoblastoma therapy from genomic and epigenetic analyses
Published: January, 2012

Abstract: Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the ret...
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Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.
Published: January, 2012

Abstract: T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we report the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 g...
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Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation.
Published: January, 2012

Abstract: Nutrient deprivation or starvation frequently correlates with amino acid limitation. Amino acid starvation initiates a signal transduction cascade starting with the activation of the kinase GCN2 phosphorylation of eukaryotic initiation factor 2, g...
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Nonoverlapping functions of the Polycomb group Cbx family of proteins in embryonic stem cells.
Published: January, 2012

Abstract: Polycomb group proteins are essential regulators of cell fate decisions during embryogenesis. In mammals, at least five different Cbx proteins (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8) are known to associate with the core Polycomb repressive complex 1 (P...
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The prosensory function of sox2 in the chicken inner ear relies on the direct regulation of atoh1.
Published: January, 2012

Abstract: The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to expl...
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Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity.
Published: December, 2011

Abstract: The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is r...
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High-Mobility Group A1 Protein: A New Coregulator of Peroxisome Proliferator-Activated Receptor-γ-Mediated Transrepression in the Vasculature.
Published: December, 2011

Abstract: Rationale:The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of gene transcription in vascular cells and mediates the vascular protection observed with antidiabetic glitazones.Objective:To determine...
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The little elongation complex regulates small nuclear RNA transcription.
Published: December, 2011

Abstract: Eleven-nineteen lysine-rich leukemia (ELL) participates in the super elongation complex (SEC) with the RNA polymerase II (Pol II) CTD kinase P-TEFb. SEC is a key regulator in the expression of HOX genes in mixed lineage leukemia (MLL)-based hemato...
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Caenorhabditis elegans Heterochromatin Protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism.
Published: December, 2011

Abstract: ABSTRACT: BACKGROUND: Heterochromatin protein 1 (HP1) family proteins have a well-characterized role in heterochromatin packaging and gene regulation. Their function in organismal development, however, is less well understood. Here we used genome...
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Characterization of a proximal Sp1 response element in the mouse Dlk2 gene promoter.
Published: December, 2011

Abstract: ABSTRACT: BACKGROUND: DLK2 is an EGF-like membrane protein, closely related to DLK1, which is involved in adipogenesis. Both proteins interact with the NOTCH1 receptor and are able to modulate its activation. The expression of the gene Dlk2 is co...
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A small molecule differentiation inducer increases insulin production by pancreatic β cells.
Published: December, 2011

Abstract: New drugs for preserving and restoring pancreatic β-cell function are critically needed for the worldwide epidemic of type 2 diabetes and the cure for type 1 diabetes. We previously identified a family of neurogenic 3,5-disubstituted isoxazoles (I...
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Second order regulator Collier directly controls intercalary-specific segment polarity gene expression.
Published: December, 2011

Abstract: In Drosophila, trunk metamerization is established by a cascade of segmentation gene activities: the gap genes, the pair rule genes, and the segment polarity genes. In the anterior head, metamerization requires also gap-like genes and segment pola...
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Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila.
Published: December, 2011

Abstract: Cancer stem cells (CSCs) are postulated to be a small subset of tumor cells with tumor-initiating ability that shares features with normal tissue-specific stem cells. The origin of CSCs and the mechanisms underlying their genesis are poorly unders...
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The Chromatin Binding Protein HMGN1 Regulates the Expression of Methyl CpG Binding Protein 2 (MECP2) and Affects the Behavior of Mice.
Published: December, 2011

Abstract: High Mobility Group N1 protein (HMGN1), a nucleosomal binding protein that affects the structure and function of chromatin, is encoded by a gene located on chromosome 21, and is overexpressed in Down syndrome, one of the most prevalent genomic dis...
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Genome-wide profiling of LXR, RXR and PPARα in mouse liver reveals extensive sharing of binding sites.
Published: December, 2011

Abstract: The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia...
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Comprehensive genome-wide protein-DNA interactions detected at single-nucleotide resolution.
Published: December, 2011

Abstract: Chromatin immunoprecipitation (ChIP-chip and ChIP-seq) assays identify where proteins bind throughout a genome. However, DNA contamination and DNA fragmentation heterogeneity produce false positives (erroneous calls) and imprecision in mapping. Co...
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A distinct mechanism for coactivator versus corepressor function by histone methyltransferase G9a in transcriptional regulation.
Published: December, 2011

Abstract: Histone methyltransferase G9a has been understood primarily as a corepressor of gene expression, but we showed previously that G9a positively regulates nuclear receptor-mediated transcription in reporter gene assays. Here, we show that endogenous ...
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Notch Activation of Jagged1 Contributes to the Assembly of the Arterial Wall
Published: December, 2011

Abstract: BACKGROUND: Notch signaling in vascular smooth muscle precursors is required for smooth muscle differentiation. Jagged1 expression on endothelium activates Notch in vascular smooth muscle precursors including those of neural crest origin to initi...
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NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression.
Published: December, 2011

Abstract: Pluripotent cells possess the ability to differentiate into any cell type. Commitment to differentiate into specific lineages requires strict control of gene expression to coordinate the downregulation of lineage inappropriate genes while enabling...
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Etsrp/Etv2 Is Directly Regulated by Foxc1a/b in the Zebrafish Angioblast.
Published: December, 2011

Abstract: Rationale:Endothelial cells are developmentally derived from angioblasts specified in the mesodermal germ cell layer. The transcription factor etsrp/etv2 is at the top of the known genetic hierarchy for angioblast development. The transcriptional ...
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Novel insights into the regulation of antioxidant-response-element-mediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2.
Published: December, 2011

Abstract: A central mechanism in cellular defence against oxidative or electrophilic stress is mediated by transcriptional induction of genes via the ARE (antioxidant-response element), a cis-acting sequence present in the regulatory regions of genes involv...
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Role of farnesoid X receptor (FXR) in the process of differentiation of bone marrow stromal cells into osteoblasts.
Published: December, 2011

Abstract: Bone tissue contains bile acids which accumulate from serum and which can be released in large amounts in the bone microenvironment during bone resorption. However, the direct effects of bile acids on bone cells remain largely unexplored. Bile aci...
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Distinct Epigenomic Features in End-Stage Failing Human Hearts
Published: November, 2011

Abstract: Background—The epigenome refers to marks on the genome, including DNA methylation and histone modifications, that regulate the expression of underlying genes. A consistent profile of gene expression changes in end-stage cardiomyopathy led us to hy...
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Generation and characterization of rat and mouse monoclonal antibodies specific for MeCP2 and their use in X-inactivation studies.
Published: November, 2011

Abstract: Methyl CpG binding protein 2 (MeCP2) binds DNA, and has a preference for methylated CpGs and, hence, in cells, it accumulates in heterochromatin. Even though it is expressed ubiquitously MeCP2 is particularly important during neuronal maturation. ...
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Genomic Maps of Long Noncoding RNA Occupancy Reveal Principles of RNA-Chromatin Interactions.
Published: November, 2011

Abstract: Long noncoding RNAs (lncRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retriev...
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Human tRNA genes function as chromatin insulators
Published: November, 2011

Abstract: nsulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs ar...
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The forkhead transcription factor FOXK2 promotes AP-1-mediated transcriptional regulation.
Published: November, 2011

Abstract: The transcriptional control circuitry in eukaryotic cells is complex and is orchestrated by combinatorially acting transcription factors. Forkhead transcription factors often function in concert with heterotypic transcription factors to specify di...
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