Tags | Diagenode

Chitosan nano-vehicles as biocompatible delivering tools for a newAg(I)curcuminoid-Gboxin analog complex in cancer and inflammation therapy
Published: December, 2020

Abstract: A novel anticancer and anti-inflammatory agent based on hybrid curcuminoid-Gboxin analog (FLLL49-GbA) and its macromolecular silver(I) complex (Ag(I)FLLL49-GbA) have successfully synthesized. In addition, chitosan nanoparticles (CNPs) were used to...
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Enhancer hijacking determines extrachromosomal circular MYCN ampliconarchitecture in neuroblastoma.
Published: November, 2020

Abstract: MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functio...
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Epigenome-wide association study for pesticide (Permethrin and DEET)induced DNA methylation epimutation biomarkers for specifictransgenerational disease.
Published: November, 2020

Abstract: BACKGROUND: Permethrin and N,N-diethyl-meta-toluamide (DEET) are the pesticides and insect repellent most commonly used by humans. These pesticides have been shown to promote the epigenetic transgenerational inheritance of disease in rats. The cur...
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Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level.
Published: November, 2020

Abstract: Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replicat...
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Increased H3K4me3 methylation and decreased miR-7113-5p expression lead toenhanced Wnt/β-catenin signaling in immune cells from PTSD patientsleading to inflammatory phenotype.
Published: November, 2020

Abstract: BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder accompanied by chronic peripheral inflammation. What triggers inflammation in PTSD is currently unclear. In the present study, we identified potential defects in signaling ...
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A histone H3.3K36M mutation in mice causes an imbalance of histonemodifications and defects in chondrocyte differentiation.
Published: November, 2020

Abstract: Histone lysine-to-methionine (K-to-M) mutations have been identified as driver mutations in human cancers. Interestingly, these 'oncohistone' mutations inhibit the activity of histone methyltransferases. Therefore, they can potentially be used as ...
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The histone H2B ubiquitin ligase RNF40 is required for HER2-drivenmammary tumorigenesis.
Published: October, 2020

Abstract: The HER2-positive breast cancer subtype (HER2-BC) displays a particularly aggressive behavior. Anti-HER2 therapies have significantly improved the survival of patients with HER2-BC. However, a large number of patients become refractory to current ...
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StE(z)2, a Polycomb group methyltransferase and deposition of H3K27me3 andH3K4me3 regulate the expression of tuberization genes in potato.
Published: October, 2020

Abstract: Polycomb Repressive Complex (PRC) group proteins regulate various developmental processes in plants by repressing the target genes via H3K27 trimethylation, whereas their function is antagonized by Trithorax group proteins-mediated H3K4 trimethyla...
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Priming for enhanced ARGONAUTE2 activation accompanies induced resistanceto cucumber mosaic virus in Arabidopsis thaliana.
Published: October, 2020

Abstract: Systemic acquired resistance (SAR) is a broad-spectrum disease resistance response that can be induced upon infection from pathogens or by chemical treatment, such as with benzo-(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH). SAR invo...
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Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .
Published: October, 2020

Abstract: Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic ...
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NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.
Published: October, 2020

Abstract: De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, whic...
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UTX/KDM6A suppresses AP-1 and a gliogenesis program during neuraldifferentiation of human pluripotent stem cells.
Published: September, 2020

Abstract: BACKGROUND: UTX/KDM6A is known to interact and influence multiple different chromatin modifiers to promote an open chromatin environment to facilitate gene activation, but its molecular activities in developmental gene regulation remain unclear. R...
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Between-Generation Phenotypic and Epigenetic Stability in a Clonal Snail.
Published: September, 2020

Abstract: Epigenetic variation might play an important role in generating adaptive phenotypes by underpinning within-generation developmental plasticity, persistent parental effects of the environment (e.g., transgenerational plasticity), or heritable epige...
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Frataxin gene editing rescues Friedreich's ataxia pathology in dorsal rootganglia organoid-derived sensory neurons.
Published: August, 2020

Abstract: Friedreich's ataxia (FRDA) is an autosomal-recessive neurodegenerative and cardiac disorder which occurs when transcription of the FXN gene is silenced due to an excessive expansion of GAA repeats into its first intron. Herein, we generate dorsal ...
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Combined treatment with CBP and BET inhibitors reverses inadvertentactivation of detrimental super enhancer programs in DIPG cells.
Published: August, 2020

Abstract: Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K...
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A gene therapy for inherited blindness using dCas9-VPR–mediatedtranscriptional activation
Published: August, 2020

Abstract: Catalytically inactive dCas9 fused to transcriptional activators (dCas9-VPR) enables activation of silent genes. Many disease genes have counterparts, which serve similar functions but are expressed in distinct cell types. One attractive option to...
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Differential Expression of Members of SOX Family of Transcription Factorsin Failing Human Hearts
Published: August, 2020

Abstract: Background: The Sry-related high-mobility-group box (SOX) gene family, with 20 known transcription factors in humans, plays essential roles during development and in many disease processes. Several SOX proteins, e.g., SOX4, SOX11, and SOX9, are re...
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The transcription factor scleraxis differentially regulates gene expressionin tenocytes isolated at different developmental stages.
Published: August, 2020

Abstract: The transcription factor scleraxis (SCX) is expressed throughout tendon development and plays a key role in directing tendon wound healing. However, little is known regarding its role in fetal or young postnatal tendons, stages in development that...
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Inhibition of the SET8 Pathway Ameliorates Lung Fibrosis Even ThroughFibroblast Dedifferentiation
Published: August, 2020

Abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiopathogenesis. The activation of extracellular matrix (ECM)-producing myofibroblasts plays a key role in fibrotic tissue remodeling. The dedifferentiation of myofibroblasts ...
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PR-DUB maintains expression of critical genes through FOXK1/2 andASXL1/2/3-dependent recruitment to chromatin and H2AK119ub1deubiquitination.
Published: August, 2020

Abstract: Polycomb group proteins are important for maintaining gene expression patterns and cell identity in metazoans. The mammalian Polycomb repressive de-ubiquitinase (PR-DUB) complexes catalyze removal of monoubiquitination on lysine 119 of histone H2A...
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Integrative Omics Analyses Reveal Epigenetic Memory in Diabetic Renal CellsRegulating Genes Associated With Kidney Dysfunction.
Published: August, 2020

Abstract: Diabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end-stage renal failure. Epigenetics has been associated with metabolic memory, in which prior periods of hyperglycemia enhance the future risk of developin...
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Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.
Published: August, 2020

Abstract: Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel fa...
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Distinct and temporary-restricted epigenetic mechanisms regulate human αβ and γδ T cell development
Published: July, 2020

Abstract: The development of TCRαβ and TCRγδ T cells comprises a step-wise process in which regulatory events control differentiation and lineage outcome. To clarify these mechanisms, we employed RNA-sequencing, ATAC-sequencing and Ch...
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OxLDL-mediated immunologic memory in endothelial cells.
Published: July, 2020

Abstract: Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLD...
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The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis.
Published: July, 2020

Abstract: Psoriasis is a frequent inflammatory skin disease characterized by keratinocyte hyperproliferation and a disease-related infiltration of immune cells. Here, we identified a novel pro-inflammatory signaling pathway driven by the cyclin-dependent ki...
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The Human Integrator Complex Facilitates Transcriptional Elongation by Endonucleolytic Cleavage of Nascent Transcripts.
Published: July, 2020

Abstract: Transcription by RNA polymerase II (RNAPII) is pervasive in the human genome. However, the mechanisms controlling transcription at promoters and enhancers remain enigmatic. Here, we demonstrate that Integrator subunit 11 (INTS11), the catalytic su...
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Prostate cancer reactivates developmental epigenomic programs during metastatic progression.
Published: July, 2020

Abstract: Epigenetic processes govern prostate cancer (PCa) biology, as evidenced by the dependency of PCa cells on the androgen receptor (AR), a prostate master transcription factor. We generated 268 epigenomic datasets spanning two state transitions-from ...
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MeCP2 regulates gene expression through recognition of H3K27me3.
Published: July, 2020

Abstract: MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA in the regulation of gene expression is well established. However, the widespread distribution of MeCP2 sug...
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Epigenetic, transcriptional and phenotypic responses in Daphnia magna exposed to low-level ionizing radiation
Published: July, 2020

Abstract: Ionizing radiation is known to induce oxidative stress and DNA damage as well as epigenetic effects in aquatic organisms. Epigenetic changes can be part of the adaptive responses to protect organisms from radiation-induced damage, or act as driver...
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Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination.
Published: July, 2020

Abstract: Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann ce...
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Premature termination codons in the gene cause reduced local mRNA synthesis.
Published: July, 2020

Abstract: Duchenne muscular dystrophy (DMD) is caused by mutations in the gene leading to the presence of premature termination codons (PTC). Previous transcriptional studies have shown reduced DMD transcript levels in DMD patient and animal model muscles w...
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Identification of Novel Molecular Markers of Human Th17 Cells.
Published: July, 2020

Abstract: Th17 cells are important players in host defense against pathogens such as , , and . Th17 cell-mediated inflammation, under certain conditions in which balance in the immune system is disrupted, is the underlying pathogenic mechanism of certain au...
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FiTAc-seq: fixed-tissue ChIP-seq for H3K27ac profiling and super-enhancer analysis of FFPE tissues.
Published: June, 2020

Abstract: Fixed-tissue ChIP-seq for H3K27 acetylation (H3K27ac) profiling (FiTAc-seq) is an epigenetic method for profiling active enhancers and promoters in formalin-fixed, paraffin-embedded (FFPE) tissues. We previously developed a modified ChIP-seq proto...
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The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications.
Published: June, 2020

Abstract: Although more and more children are born by Assisted Reproductive Technologies (ART), ART safety has not fully been demonstrated. Notably, ART could disturb the delicate step of implantation, and trigger placenta-related adverse outcomes with pote...
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Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes.
Published: June, 2020

Abstract: Definitive diagnosis of intracranial tumors relies on tissue specimens obtained by invasive surgery. Noninvasive diagnostic approaches provide an opportunity to avoid surgery and mitigate unnecessary risk to patients. In the present study, we show...
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Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes.
Published: June, 2020

Abstract: Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a highly sensitive assay capable of detecting early-s...
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Epigenetic priming by Dppa2 and 4 in pluripotency facilitates multi-lineage commitment.
Published: June, 2020

Abstract: How the epigenetic landscape is established in development is still being elucidated. Here, we uncover developmental pluripotency associated 2 and 4 (DPPA2/4) as epigenetic priming factors that establish a permissive epigenetic landscape at a subs...
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Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition.
Published: June, 2020

Abstract: A subset of lung adenocarcinomas is driven by the EML4-ALK translocation. Even though ALK inhibitors in the clinic lead to excellent initial responses, acquired resistance to these inhibitors due to on-target mutations or parallel pathway alterati...
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Genomic deregulation of PRMT5 supports growth and stress tolerance in chronic lymphocytic leukemia.
Published: June, 2020

Abstract: Patients suffering from chronic lymphocytic leukemia (CLL) display highly diverse clinical courses ranging from indolent cases to aggressive disease, with genetic and epigenetic features resembling this diversity. Here, we developed a comprehensiv...
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DNA methylation dynamics underlie metamorphic gene regulation programs in Xenopus tadpole brain.
Published: June, 2020

Abstract: Methylation of cytosine residues in DNA influences chromatin structure and gene transcription, and its regulation is crucial for brain development. There is mounting evidence that DNA methylation can be modulated by hormone signaling. We analyzed ...
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An optimised Chromatin Immunoprecipitation (ChIP) method for starchy leaves of Nicotiana benthamiana to study histone modifications of an allotetraploid plant
Published: June, 2020

Abstract: All flowering plants have evolved through multiple rounds of polyploidy throughout the evolutionary process. Intergenomic interactions between subgenomes in polyploid plants are predicted to induce chromatin modifications such as histone modificat...
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Estrogen induces dynamic ERα and RING1B recruitment to control gene and enhancer activities in luminal breast cancer
Published: June, 2020

Abstract: RING1B, a core Polycomb repressive complex 1 subunit, is a histone H2A ubiquitin ligase essential for development. RING1B is overexpressed in patients with luminal breast cancer (BC) and recruited to actively transcribed genes and enhancers co-occ...
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Global analysis of histone modifications and long-range chromatin interactions revealed the differential cistrome changes and novel transcriptional players in human dilated cardiomyopathy.
Published: June, 2020

Abstract: BACKGROUND: Acetylation and methylation of histones alter the chromatin structure and accessibility that affect transcriptional regulators binding to enhancers and promoters. The binding of transcriptional regulators enables the interaction betwee...
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A conserved RNA degradation complex required for spreading and epigenetic inheritance of heterochromatin.
Published: June, 2020

Abstract: Heterochromatic domains containing histone H3 lysine 9 methylation (H3K9me) can be epigenetically inherited independently of underlying DNA sequence. To gain insight into the mechanisms that mediate epigenetic inheritance, we used a inducible hete...
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Intergenerationally Maintained Histone H4 Lysine 16 Acetylation Is Instructive for Future Gene Activation.
Published: June, 2020

Abstract: Before zygotic genome activation (ZGA), the quiescent genome undergoes reprogramming to transition into the transcriptionally active state. However, the mechanisms underlying euchromatin establishment during early embryogenesis remain poorly under...
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AXR1 affects DNA methylation independently of its role in regulatingmeiotic crossover localization.
Published: June, 2020

Abstract: Meiotic crossovers (COs) are important for reshuffling genetic information between homologous chromosomes and they are essential for their correct segregation. COs are unevenly distributed along chromosomes and the underlying mechanisms controllin...
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The 20S proteasome activator PA28γ controls the compaction of chromatin
Published: May, 2020

Abstract: The nuclear PA28γ is known to activate the 20S proteasome, but its precise cellular functions remains unclear. Here, we identify PA28γ as a key factor that structures heterochromatin. We find that in human cells, a fraction of PA28&gam...
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Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene.
Published: May, 2020

Abstract: The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity...
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Measuring Histone Modifications in the Human Parasite Schistosoma mansoni
Published: May, 2020

Abstract: DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by ...
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Histone post-translational modifications in Silene latifolia X and Y chromosomes suggest a mammal-like dosage compensation system
Published: May, 2020

Abstract: Silene latifolia is a model organism to study evolutionary young heteromorphic sex chromosome evolution in plants. Previous research indicates a Y-allele gene degeneration and a dosage compensation system already operating. Here, we propose an epi...
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AP-1 controls the p11-dependent antidepressant response.
Published: May, 2020

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed drugs for mood disorders. While the mechanism of SSRI action is still unknown, SSRIs are thought to exert therapeutic effects by elevating extracellular serotonin level...
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2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer.
Published: May, 2020

Abstract: Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased charact...
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Attenuated Epigenetic Suppression of Muscle Stem Cell Necroptosis Is Required for Efficient Regeneration of Dystrophic Muscles.
Published: May, 2020

Abstract: Somatic stem cells expand massively during tissue regeneration, which might require control of cell fitness, allowing elimination of non-competitive, potentially harmful cells. How or if such cells are removed to restore organ function is not full...
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β-Glucan Induces Protective Trained Immunity against Mycobacterium tuberculosis Infection: A Key Role for IL-1.
Published: May, 2020

Abstract: β-glucan is a potent inducer of epigenetic and functional reprogramming of innate immune cells, a process called "trained immunity," resulting in an enhanced host response against secondary infections. We investigate whether β-glucan exp...
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DNA methylation enzymes and PRC1 restrict B-cell Epstein-Barr virus oncoprotein expression.
Published: May, 2020

Abstract: To accomplish the remarkable task of lifelong infection, the Epstein-Barr virus (EBV) switches between four viral genome latency and lytic programmes to navigate the B-cell compartment and evade immune responses. The transforming programme, consis...
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DNA methylation variation in the brain of laying hens in relation to differential behavioral patterns
Published: May, 2020

Abstract: Domesticated animals are unique to investigate the contribution of genetic and non-genetic factors to specific phenotypes. Among non-genetic factors involved in phenotype formation are epigenetic mechanisms. Here we aimed to identify whether relat...
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TET3 controls the expression of the H3K27me3 demethylase Kdm6b during neural commitment.
Published: May, 2020

Abstract: The acquisition of cell identity is associated with developmentally regulated changes in the cellular histone methylation signatures. For instance, commitment to neural differentiation relies on the tightly controlled gain or loss of H3K27me3, a h...
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Homer1a Undergoes Bimodal Transcriptional Regulation by CREB and the Circadian Clock.
Published: May, 2020

Abstract: Accumulating evidence points to a significant link between disrupted circadian rhythms and neuronal disfunctions, though the molecular mechanisms underlying this connection are virtually unexplored. The transcript Homer1a, an immediate early gene ...
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Revisiting promyelocytic leukemia protein targeting by human cytomegalovirus immediate-early protein 1.
Published: May, 2020

Abstract: Promyelocytic leukemia (PML) bodies are nuclear organelles implicated in intrinsic and innate antiviral defense. The eponymous PML proteins, central to the self-organization of PML bodies, and other restriction factors found in these organelles ar...
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In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.
Published: May, 2020

Abstract: Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progressio...
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The domesticated transposase ALP2 mediates formation of a novel Polycomb protein complex by direct interaction with MSI1, a core subunit of Polycomb Repressive Complex 2 (PRC2).
Published: May, 2020

Abstract: A large fraction of plant genomes is composed of transposable elements (TE), which provide a potential source of novel genes through "domestication"-the process whereby the proteins encoded by TE diverge in sequence, lose their ability to catalyse...
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Genomic Profiling by ALaP-Seq Reveals Transcriptional Regulation by PML Bodies through DNMT3A Exclusion.
Published: April, 2020

Abstract: The promyelocytic leukemia (PML) body is a phase-separated nuclear structure physically associated with chromatin, implying its crucial roles in genome functions. However, its role in transcriptional regulation is largely unknown. We developed APE...
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Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis.
Published: April, 2020

Abstract: Tissue-resident and recruited macrophages contribute to both host defense and pathology. Multiple macrophage phenotypes are represented in diseased tissues, but we lack deep understanding of mechanisms controlling diversification. Here, we investi...
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SETDB2 promoted breast cancer stem cell maintenance by interaction with and stabilization of ΔNp63α protein
Published: April, 2020

Abstract: The histone H3K9 methyltransferase SETDB2 is involved in cell cycle dysregulation in acute leukemia and has oncogenic roles in gastric cancer. In our study, we found that SETDB2 plays essential roles in breast cancer stem cell maintenance. Deplete...
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Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction.
Published: April, 2020

Abstract: Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRN...
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Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer.
Published: April, 2020

Abstract: The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transcriptomic landscapes of...
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An epigenetic map of malaria parasite development from host to vector.
Published: April, 2020

Abstract: The malaria parasite replicates asexually in the red blood cells of its vertebrate host employing epigenetic mechanisms to regulate gene expression in response to changes in its environment. We used chromatin immunoprecipitation followed by sequen...
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The TGF-β profibrotic cascade targets ecto-5'-nucleotidase gene in proximal tubule epithelial cells and is a traceable marker of progressive diabetic kidney disease.
Published: April, 2020

Abstract: Progressive diabetic nephropathy (DN) and loss of renal function correlate with kidney fibrosis. Crosstalk between TGF-β and adenosinergic signaling contributes to the phenotypic transition of cells and to renal fibrosis in DN models. We eval...
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Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin.
Published: April, 2020

Abstract: Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled...
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Endogenous retroviruses are a source of enhancers with oncogenic potential in acute myeloid leukaemia
Published: April, 2020

Abstract: Acute myeloid leukemia (AML) is a highly aggressive hematopoietic malignancy, defined by a series of genetic and epigenetic alterations, which result in deregulation of transcriptional networks. One understudied but important source of transcripti...
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TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition.
Published: March, 2020

Abstract: Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose patients to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its cont...
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CRISPR-based gene knockout screens reveal deubiquitinases involved in HIV-1 latency in two Jurkat cell models.
Published: March, 2020

Abstract: The major barrier to a HIV-1 cure is the persistence of latent genomes despite treatment with antiretrovirals. To investigate host factors which promote HIV-1 latency, we conducted a genome-wide functional knockout screen using CRISPR-Cas9 in a HI...
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Differential modulation of the androgen receptor for prostate cancer therapy depends on the DNA response element.
Published: March, 2020

Abstract: Androgen receptor (AR) action is a hallmark of prostate cancer (PCa) with androgen deprivation being standard therapy. Yet, resistance arises and aberrant AR signaling promotes disease. We sought compounds that inhibited genes driving cancer but n...
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High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase.
Published: March, 2020

Abstract: Cellular levels of ribonucleoside triphosphates (rNTPs) are much higher than those of deoxyribonucleoside triphosphates (dNTPs), thereby influencing the frequency of incorporation of ribonucleoside monophosphates (rNMPs) by DNA polymerases (Pol) i...
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Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor.
Published: March, 2020

Abstract: Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nan...
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LXR Activation Induces a Proinflammatory Trained Innate Immunity-Phenotype in Human Monocytes
Published: March, 2020

Abstract: The concept of trained innate immunity describes a long-term proinflammatory memory in innate immune cells. Trained innate immunity is regulated through reprogramming of cellular metabolic pathways including cholesterol and fatty acid synthesis. H...
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CDK7 Inhibition is Effective in all the Subtypes of Breast Cancer: Determinants of Response and Synergy with EGFR Inhibition.
Published: March, 2020

Abstract: CDK7, a transcriptional cyclin-dependent kinase, is emerging as a novel cancer target. Triple-negative breast cancers (TNBC) but not estrogen receptor-positive (ER+) breast cancers have been reported to be uniquely sensitive to the CDK7 inhibitor ...
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ChromID identifies the protein interactome at chromatin marks.
Published: March, 2020

Abstract: Chromatin modifications regulate genome function by recruiting proteins to the genome. However, the protein composition at distinct chromatin modifications has yet to be fully characterized. In this study, we used natural protein domains as modula...
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HDAC3 functions as a positive regulator in Notch signal transduction.
Published: February, 2020

Abstract: Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the N...
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A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment.
Published: February, 2020

Abstract: Toxoplasma gondii has a complex life cycle that is typified by asexual development that takes place in vertebrates, and sexual reproduction, which occurs exclusively in felids and is therefore less studied. The developmental transitions rely on ch...
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Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown/Beige Adipocytes
Published: February, 2020

Abstract: Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi-omics data, transferrin...
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Recombination may occur in the absence of transcription in the immunoglobulin heavy chain recombination centre.
Published: February, 2020

Abstract: Developing B cells undergo V(D)J recombination to generate a vast repertoire of Ig molecules. V(D)J recombination is initiated by the RAG1/RAG2 complex in recombination centres (RCs), where gene segments become accessible to the complex. Whether t...
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Alteration of CTCF-associated chromatin neighborhood inhibits TAL1-driven oncogenic transcription program and leukemogenesis.
Published: February, 2020

Abstract: Aberrant activation of the TAL1 is associated with up to 60% of T-ALL cases and is involved in CTCF-mediated genome organization within the TAL1 locus, suggesting that CTCF boundary plays a pathogenic role in T-ALL. Here, we show that -31-Kb CTCF ...
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DNA Methylation Editing by CRISPR-guided Excision of 5-Methylcytosine.
Published: February, 2020

Abstract: Tools for actively targeted DNA demethylation are required to increase our knowledge about regulation and specific functions of this important epigenetic modification. DNA demethylation in mammals involves TET-mediated oxidation of 5-methylcytosin...
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Widespread loss of the silencing epigenetic mark H3K9me3 in astrocytes and neurons along with hippocampal-dependent cognitive impairment in C9orf72 BAC transgenic mice.
Published: February, 2020

Abstract: BACKGROUND: Hexanucleotide repeat expansions of the GC motif in a non-coding region of the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Tissues from C9ALS/FTD patients and...
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Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.
Published: February, 2020

Abstract: BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect g...
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Targeting Macrophage Histone H3 Modification as a Leishmania Strategy to Dampen the NF-κB/NLRP3-Mediated Inflammatory Response.
Published: February, 2020

Abstract: Aberrant macrophage activation during intracellular infection generates immunopathologies that can cause severe human morbidity. A better understanding of immune subversion strategies and macrophage phenotypic and functional responses is necessary...
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Threonine phosphorylation of IκBζ mediates inhibition of selective proinflammatory target genes.
Published: February, 2020

Abstract: Transcription factors of the NF-κB family play a crucial role for immune responses by activating the expression of chemokines, cytokines and antimicrobial peptides involved in pathogen clearance. IκBζ, an atypical nuclear Iκ...
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Polycomb Group Proteins Regulate Chromatin Architecture in Mouse Oocytes and Early Embryos.
Published: February, 2020

Abstract: In mammals, chromatin organization undergoes drastic reorganization during oocyte development. However, the dynamics of three-dimensional chromatin structure in this process is poorly characterized. Using low-input Hi-C (genome-wide chromatin conf...
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Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex.
Published: February, 2020

Abstract: The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and th...
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Tissue alarmins and adaptive cytokine induce dynamic and distinct transcriptional responses in tissue-resident intraepithelial cytotoxic T lymphocytes.
Published: February, 2020

Abstract: The respective effects of tissue alarmins interleukin (IL)-15 and interferon beta (IFNβ), and IL-21 produced by T cells on the reprogramming of cytotoxic T lymphocytes (CTLs) that cause tissue destruction in celiac disease is poorly understoo...
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Replicational Dilution of H3K27me3 in Mammalian Cells and the Role of Poised Promoters.
Published: January, 2020

Abstract: Polycomb repressive complex 2 (PRC2) places H3K27me3 at developmental genes and is causally implicated in keeping bivalent genes silent. It is unclear if that silence requires minimum H3K27me3 levels and how the mark transmits faithfully across ma...
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Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome.
Published: January, 2020

Abstract: Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phen...
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miR-155 inhibits mitophagy through suppression of BAG5, a partner protein of PINK1.
Published: January, 2020

Abstract: Removal of dysfunctional mitochondria is essential step to maintain normal cell physiology, and selective autophagy in mitochondria, called mitophagy, plays a critical role in quality control of mitochondria. While in several diseases and aging, d...
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AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation.
Published: January, 2020

Abstract: Activation of T cells is dependent on the organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of c...
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A comprehensive epigenomic analysis of phenotypically distinguishable, genetically identical female and male Daphnia pulex.
Published: January, 2020

Abstract: BACKGROUND: Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and fem...
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Analysis of Histone Modifications in Rodent Pancreatic Islets by Native Chromatin Immunoprecipitation.
Published: January, 2020

Abstract: The islets of Langerhans are clusters of cells dispersed throughout the pancreas that produce several hormones essential for controlling a variety of metabolic processes, including glucose homeostasis and lipid metabolism. Studying the transcripti...
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TIP60/P400/H4K12ac Plays a Role as a Heterochromatin Back-up Skeleton inBreast Cancer.
Published: January, 2020

Abstract: BACKGROUND/AIM: In breast cancer, initiation of carcinogenesis leads to epigenetic dysregulation, which can lead for example to the loss of the heterochromatin skeleton SUV39H1/H3K9me3/HP1 or the supposed secondary skeleton TIP60/P400/H4K12ac/BRD ...
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The Inhibition of the Histone Methyltransferase EZH2 by DZNEP or SiRNA Demonstrates Its Involvement in MGMT, TRA2A, RPS6KA2, and U2AF1 Gene Regulation in Prostate Cancer.
Published: December, 2019

Abstract: In France, prostate cancer is the most common cancer in men (Bray et al., 2018). Previously, our team has reported the involvement of epigenetic factors in prostate cancer (Ngollo et al., 2014, 2017). The histone 3 lysine 27 trimethylation (H3K27m...
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Charting the cis-regulome of activated B cells by coupling structural and functional genomics.
Published: December, 2019

Abstract: Cis-regulomes underlying immune-cell-specific genomic states have been extensively analyzed by structure-based chromatin profiling. By coupling such approaches with a high-throughput enhancer screen (self-transcribing active regulatory region sequ...
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Unraveling the role of H3K4 trimethylation and lncRNA HOTAIR in SATB1 and DUSP4-dependent survival of virulent Mycobacterium tuberculosis in macrophages
Published: December, 2019

Abstract: The modification of chromatin influences host transcriptional programs during bacterial infection, at times skewing the balance in favor of pathogen survival. To test the role of chromatin modifications during Mycobacterium tuberculosis infection,...
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Allelic H3K27me3 to allelic DNA methylation switch maintains noncanonical imprinting in extraembryonic cells
Published: December, 2019

Abstract: Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation–dependent (canonical) imprinting is relatively stable during development, the recently found oocyte-derived H3K27me3-mediated n...
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Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.
Published: December, 2019

Abstract: One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to ...
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H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.
Published: December, 2019

Abstract: Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation...
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Inhibition of Histone Demethylases LSD1 and UTX Regulates ERα Signaling in Breast Cancer.
Published: December, 2019

Abstract: In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-locali...
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Trained immunity modulates inflammation-induced fibrosis.
Published: December, 2019

Abstract: Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or ...
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Mkt1 is required for RNAi-mediated silencing and establishment of heterochromatin in fission yeast.
Published: December, 2019

Abstract: Constitutive domains of repressive heterochromatin are maintained within the fission yeast genome through self-reinforcing mechanisms involving histone methylation and small RNAs. Non-coding RNAs generated from heterochromatic regions are processe...
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A Study of High-Grade Serous Ovarian Cancer Origins Implicates the SOX18 Transcription Factor in Tumor Development.
Published: December, 2019

Abstract: Fallopian tube secretory epithelial cells (FTSECs) are likely the main precursor cell type of high-grade serous ovarian cancers (HGSOCs), but these tumors may also arise from ovarian surface epithelial cells (OSECs). We profiled global landscapes ...
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USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer.
Published: December, 2019

Abstract: As a member of the 11-gene "death-from-cancer" gene expression signature, overexpression of the Ubiquitin-Specific Protease 22 (USP22) was associated with poor prognosis in various human malignancies. To investigate the function of USP22 in cancer...
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SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophages.
Published: December, 2019

Abstract: Sirtuins 1 and 2 (SIRT1/2) are two NAD-dependent deacetylases with major roles in inflammation. In addition to deacetylating histones and other proteins, SIRT1/2-mediated regulation is coupled with other epigenetic enzymes. Here, we investigate th...
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Sodium valproate and 5-aza-2'-deoxycytidine differentially modulate DNA demethylation in G1 phase-arrested and proliferative HeLa cells.
Published: December, 2019

Abstract: Sodium valproate/valproic acid (VPA), a histone deacetylase inhibitor, and 5-aza-2-deoxycytidine (5-aza-CdR), a DNA methyltransferase 1 (DNMT1) inhibitor, induce DNA demethylation in several cell types. In HeLa cells, although VPA leads to decreas...
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Episo: quantitative estimation of RNA 5-methylcytosine at isoform level by high-throughput sequencing of RNA treated with bisulfite.
Published: December, 2019

Abstract: MOTIVATION: RNA 5-methylcytosine (m5C) is a type of post-transcriptional modification that may be involved in numerous biological processes and tumorigenesis. RNA m5C can be profiled at single-nucleotide resolution by high-throughput sequencing of...
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MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells.
Published: November, 2019

Abstract: MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation,...
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Intra- and inter-generational changes in the cortical DNA methylome in response to therapeutic intermittent hypoxia in mice.
Published: November, 2019

Abstract: Recent evidence from our lab documents functional resilience to retinal ischemic injury in untreated mice derived from parents exposed to repetitive hypoxic conditioning (RHC) prior to breeding. To begin to understand the epigenetic basis of this ...
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R-Loops Promote Antisense Transcription across the Mammalian Genome
Published: November, 2019

Abstract: Widespread antisense long noncoding RNA (lncRNA) overlap with many protein-coding genes in mammals and emanate from gene promoter, enhancer, and termination regions. However, their origin and biological purpose remain unclear. We show that these a...
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Autoregulation of RCO by Low-Affinity Binding Modulates Cytokinin Action and Shapes Leaf Diversity.
Published: November, 2019

Abstract: Mechanisms through which the evolution of gene regulation causes morphological diversity are largely unclear. The tremendous shape variation among plant leaves offers attractive opportunities to address this question. In cruciferous plants, the RE...
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CREB5 Promotes Resistance to Androgen-Receptor Antagonists and Androgen Deprivation in Prostate Cancer.
Published: November, 2019

Abstract: Androgen-receptor (AR) inhibitors, including enzalutamide, are used for treatment of all metastatic castration-resistant prostate cancers (mCRPCs). However, some patients develop resistance or never respond. We find that the transcription factor C...
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Recurrent SMARCB1 Mutations Reveal a Nucleosome Acidic Patch Interaction Site That Potentiates mSWI/SNF Complex Chromatin Remodeling.
Published: November, 2019

Abstract: Mammalian switch/sucrose non-fermentable (mSWI/SNF) complexes are multi-component machines that remodel chromatin architecture. Dissection of the subunit- and domain-specific contributions to complex activities is needed to advance mechanistic und...
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MicroRNAs Establish the Right-Handed Dominance of the Heart Laterality Pathway in Vertebrates
Published: November, 2019

Abstract: Despite their external bilateral symmetry, vertebrates have internal left/right (L/R) asymmetries required for optimal organ function. BMP-induced epithelial to mesenchymal transition (EMT) in the lateral plate mesoderm (LPM) triggers L/R asymmetr...
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Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition.
Published: November, 2019

Abstract: Cranial radiotherapy in children has detrimental effects on cognition, mood, and social competence in young cancer survivors. Treatments harnessing hippocampal neurogenesis are currently of great relevance in this context. Lithium, a well-known mo...
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Sperm DNA Methylation Epimutation Biomarkers for Male Infertility and FSH Therapeutic Responsiveness.
Published: November, 2019

Abstract: Male factor infertility is increasing and recognized as playing a key role in reproductive health and disease. The current primary diagnostic approach is to assess sperm quality associated with reduced sperm number and motility, which has been his...
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Distinct IL-1α-responsive enhancers promote acute and coordinated changes in chromatin topology in a hierarchical manner.
Published: November, 2019

Abstract: How cytokine-driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)-1α induces acute and widespread changes in chromatin accessibility v...
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Native Chromatin Proteomics Reveals a Role for Specific Nucleoporins in Heterochromatin Organization and Maintenance.
Published: November, 2019

Abstract: Spatially and functionally distinct domains of heterochromatin and euchromatin play important roles in the maintenance of chromosome stability and regulation of gene expression, but a comprehensive knowledge of their composition is lacking. Here, ...
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Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Published: November, 2019

Abstract: Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that r...
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Methionine metabolism in health and cancer: a nexus of diet and precisionmedicine.
Published: November, 2019

Abstract: Methionine uptake and metabolism is involved in a host of cellular functions including methylation reactions, redox maintenance, polyamine synthesis and coupling to folate metabolism, thus coordinating nucleotide and redox status. Each of these fu...
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Epigenetic transgenerational inheritance of parent-of-origin allelic transmission of outcross pathology and sperm epimutations
Published: October, 2019

Abstract: Epigenetic transgenerational inheritance potentially impacts disease etiology, phenotypic variation, and evolution. An increasing number of environmental factors from nutrition to toxicants have been shown to promote the epigenetic transgeneration...
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The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.
Published: October, 2019

Abstract: Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the position that resistan...
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TET2 Regulates the Neuroinflammatory Response in Microglia.
Published: October, 2019

Abstract: Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite the central role for microglia in neuroinflammation and neurodegeneration, little is known about their epigenomic regulation of the inflammatory ...
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Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans.
Published: October, 2019

Abstract: The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss...
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CURLY LEAF regulates micro RNA activity by controlling ARGONAUTE 1 degradation in plants.
Published: October, 2019

Abstract: CURLY LEAF (CLF) encodes the methyl-transferase sub-unit of the Polycomb Repressor Complex 2 (PRC2), which regulates the expression of target genes through H3K27 tri-methylation. We isolated a new CLF mutant allele (clf-78) using a genetic screeni...
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Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons.
Published: October, 2019

Abstract: Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenera...
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Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.
Published: October, 2019

Abstract: In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene dere...
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Assaying epigenome functions of PRMTs and their substrates.
Published: September, 2019

Abstract: Among the widespread and increasing number of identified post-translational modifications (PTMs), arginine methylation is catalyzed by the protein arginine methyltransferases (PRMTs) and regulates fundamental processes in cells, such as gene regul...
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RUNX1-ETO Depletion in t(8;21) AML Leads to C/EBPα- and AP-1-Mediated Alterations in Enhancer-Promoter Interaction.
Published: September, 2019

Abstract: Acute myeloid leukemia (AML) is associated with mutations in transcriptional and epigenetic regulator genes impairing myeloid differentiation. The t(8;21)(q22;q22) translocation generates the RUNX1-ETO fusion protein, which interferes with the hem...
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Unique and Shared Epigenetic Programs of the CREBBP and EP300 Acetyltransferases in Germinal Center B Cells Reveal Targetable Dependencies in Lymphoma.
Published: September, 2019

Abstract: Inactivating mutations of the CREBBP and EP300 acetyltransferases are among the most common genetic alterations in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). Here, we examined the relationship between these two enzymes in ...
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Functional analyses of a low-penetrance risk variant rs6702619/1p21.2 associating with colorectal cancer in Polish population.
Published: September, 2019

Abstract: Several studies employed the genome-wide association (GWA) analysis of single-nucleotide polymorphisms (SNPs) to identify susceptibility regions in colorectal cancer (CRC). However, the functional studies exploring the role of associating SNPs wit...
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Relationship between osteoporosis and osteoarthritis based on DNA methylation
Published: September, 2019

Abstract: : The aim of this study was to investigate the relationship between osteoporosis and osteoarthritis by analyzing the DNA methylation in osteoporosis and osteoarthritis. The cancellous bone specimens were collected from a total of 12 hospitalized p...
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Improved double-nicking strategies for COL7A1 editing by homologous recombination
Published: September, 2019

Abstract: Current gene editing approaches for treatment of recessive dystrophic epidermolysis bullosa (RDEB), an inherited, severe form of blistering skin disease, suffer from low efficiencies and safety concerns that complicate implementation in clinical s...
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Improved Double-Nicking Strategies for COL7A1-Editing by Homologous Recombination.
Published: September, 2019

Abstract: Current gene-editing approaches for treatment of recessive dystrophic epidermolysis bullosa (RDEB), an inherited, severe form of blistering skin disease, suffer from low efficiencies and safety concerns that complicate implementation in clinical s...
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β-Glucan-Induced Trained Immunity Protects against Leishmania braziliensis Infection: a Crucial Role for IL-32.
Published: September, 2019

Abstract: American tegumentary leishmaniasis is a vector-borne parasitic disease caused by Leishmania protozoans. Innate immune cells undergo long-term functional reprogramming in response to infection or Bacillus Calmette-Guérin (BCG) vaccination vi...
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Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.
Published: September, 2019

Abstract: Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC a...
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Preparation of cfMeDIP-seq libraries for methylome profiling of plasma cell-free DNA.
Published: August, 2019

Abstract: Circulating cell-free DNA (cfDNA) comprises small DNA fragments derived from normal and tumor tissue that are released into the bloodstream. Recently, methylation profiling of cfDNA as a liquid biopsy tool has been gaining prominence due to the pr...
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BET protein targeting suppresses the PD-1/PD-L1 pathway in triple-negative breast cancer and elicits anti-tumor immune response.
Published: August, 2019

Abstract: Therapeutic strategies aiming to leverage anti-tumor immunity are being intensively investigated as they show promising results in cancer therapy. The PD-1/PD-L1 pathway constitutes an important target to restore functional anti-tumor immune respo...
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Nucleome Dynamics during Retinal Development.
Published: August, 2019

Abstract: More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-...
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Silencing of tumor-suppressive NR_023387 in renal cell carcinoma via promoter hypermethylation and HNF4A deficiency.
Published: August, 2019

Abstract: Dysregulation of the epigenetic status of long noncoding RNAs (lncRNAs) has been linked to diverse human diseases including human cancers. However, the landscape of the whole-genome methylation profile of lncRNAs and the precise roles of these lnc...
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Slc6a8-Mediated Creatine Uptake and Accumulation Reprogram Macrophage Polarization via Regulating Cytokine Responses.
Published: August, 2019

Abstract: Macrophage polarization is accompanied by drastic changes in L-arginine metabolism. Two L-arginine catalytic enzymes, iNOS and arginase 1, are well-characterized hallmark molecules of classically and alternatively activated macrophages, respective...
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Epitranscriptomic Addition of mC to HIV-1 Transcripts Regulates Viral Gene Expression.
Published: August, 2019

Abstract: How the covalent modification of mRNA ribonucleotides, termed epitranscriptomic modifications, alters mRNA function remains unclear. One issue has been the difficulty of quantifying these modifications. Using purified HIV-1 genomic RNA, we sh...
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Free heme regulates placenta growth factor through NRF2-antioxidant response signaling.
Published: August, 2019

Abstract: Free heme activates erythroblasts to express and secrete Placenta Growth Factor (PlGF), an angiogenic peptide of the VEGF family. High circulating levels of PlGF have been associated in experimental animals and in patients with sickle cell disease...
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Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.
Published: August, 2019

Abstract: Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor ...
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Functional dissection of the Sox9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture.
Published: August, 2019

Abstract: The genome is organized in three-dimensional units called topologically associating domains (TADs), through a process dependent on the cooperative action of cohesin and the DNA-binding factor CTCF. Genomic rearrangements of TADs have been shown to...
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Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors.
Published: July, 2019

Abstract: DNA methylation contributes to the maintenance of genomic integrity in somatic cells, in part through the silencing of transposable elements. In this study, we use CRISPR-Cas9 technology to delete DNMT1, the DNA methyltransferase key for DNA methy...
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Class I TCP transcription factors target the gibberellin biosynthesis gene GA20ox1 and the growth promoting genes HBI1 and PRE6 during thermomorphogenic growth in Arabidopsis.
Published: July, 2019

Abstract: Plants respond to a rise in ambient temperature by increasing the growth of petioles and hypocotyls. In this work, we show that Arabidopsis thaliana class I TEOSINTE BRANCHED 1, CYCLOIDEA, PCF (TCP) transcription factors TCP14 and TCP15 are requir...
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Aberrant expression of imprinted lncRNA MEG8 causes trophoblast dysfunction and abortion.
Published: July, 2019

Abstract: Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs whose nucleotides are longer than 200 bp. Previous studies have shown that they play an important regulatory role in many developmental processes and biological pathways. However, ...
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Development and epigenetic plasticity of murine Müller glia.
Published: July, 2019

Abstract: The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progen...
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The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.
Published: July, 2019

Abstract: The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which s...
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Elevated cyclic-AMP represses expression of exchange protein activated by cAMP (EPAC1) by inhibiting YAP-TEAD activity and HDAC-mediated histone deacetylation.
Published: June, 2019

Abstract: Ligand-induced activation of Exchange Protein Activated by cAMP-1 (EPAC1) is implicated in numerous physiological and pathological processes, including cardiac fibrosis where changes in EPAC1 expression have been detected. However, little is known...
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Genome-wide methylation in alcohol use disorder subjects: implications for an epigenetic regulation of the cortico-limbic glucocorticoid receptors (NR3C1).
Published: June, 2019

Abstract: Environmental factors, including substance abuse and stress, cause long-lasting changes in the regulation of gene expression in the brain via epigenetic mechanisms, such as DNA methylation. We examined genome-wide DNA methylation patterns in the p...
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The alarmin S100A9 hampers osteoclast differentiation from human circulating precursors by reducing the expression of RANK.
Published: June, 2019

Abstract: The alarmin S100A8/A9 is implicated in sterile inflammation-induced bone resorption and has been shown to increase the bone-resorptive capacity of mature osteoclasts. Here, we investigated the effects of S100A9 on osteoclast differentiation from h...
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Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids.
Published: June, 2019

Abstract: The deubiquitinating enzyme BAP1 is a tumor suppressor, among others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate histone H2AK119. We introduce BAP1 loss-of-funct...
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Twist2 amplification in rhabdomyosarcoma represses myogenesis and promotes oncogenesis by redirecting MyoD DNA binding.
Published: June, 2019

Abstract: Rhabdomyosarcoma (RMS) is an aggressive pediatric cancer composed of myoblast-like cells. Recently, we discovered a unique muscle progenitor marked by the expression of the Twist2 transcription factor. Genomic analyses of 258 RMS patient tumors un...
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Preformed chromatin topology assists transcriptional robustness of during limb development.
Published: May, 2019

Abstract: Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of gene expression in space and time. However, in some cases, proximity coincides with gene activation, whereas, in others, preform...
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Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy.
Published: May, 2019

Abstract: Schwann cells ensure efficient nerve impulse conduction in the peripheral nervous system. Their development is accompanied by defined chromatin changes, including variant histone deposition and redistribution. To study the importance of variant hi...
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Life-Long AAV-Mediated CRISPR Genome Editing in Dystrophic Heart Improves Cardiomyopathy without Causing Serious Lesions in mdx Mice.
Published: May, 2019

Abstract: Previous studies from others and us have demonstrated that CRISPR genome editing could offer a promising therapeutic strategy to restore dystrophin expression and function in the skeletal muscle and heart of Duchenne muscular dystrophy (DMD) mouse...
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Acetate Promotes T Cell Effector Function during Glucose Restriction.
Published: May, 2019

Abstract: Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell fun...
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Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas.
Published: May, 2019

Abstract: High-grade gliomas defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogeni...
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BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models.
Published: May, 2019

Abstract: Drug-tolerant "persister" tumor cells underlie emergence of drug-resistant clones and contribute to relapse and disease progression. Here we report that resistance to the BCL-2 targeting drug ABT-199 in models of mantle cell lymphoma and double-hi...
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Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers.
Published: May, 2019

Abstract: The cardiogenic transcription factors (TFs) Mef2c, Gata4, and Tbx5 can directly reprogram fibroblasts to induced cardiac-like myocytes (iCLMs), presenting a potential source of cells for cardiac repair. While activity of these TFs is enhanced by H...
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Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner.
Published: May, 2019

Abstract: BACKGROUND: Rewriting of the epigenome has risen as a promising alternative to gene editing for precision medicine. In nature, epigenetic silencing can result in complete attenuation of target gene expression over multiple mitotic divisions. Howev...
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Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.
Published: May, 2019

Abstract: The gene regulatory network (GRN) of naive mouse embryonic stem cells (ESCs) must be reconfigured to enable lineage commitment. TCF3 sanctions rewiring by suppressing components of the ESC transcription factor circuitry. However, TCF3 depletion on...
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The Chromatin Factor HNI9 and ELONGATED HYPOCOTYL5 Maintain ROS Homeostasis under High Nitrogen Provision.
Published: May, 2019

Abstract: Reactive oxygen species (ROS) can accumulate in cells at excessive levels, leading to unbalanced redox states and to potential oxidative stress, which can have damaging effects on the molecular components of plant cells. Several environmental cond...
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Long-range interactions between topologically associating domains shape the four-dimensional genome during differentiation.
Published: May, 2019

Abstract: Genomic information is selectively used to direct spatial and temporal gene expression during differentiation. Interactions between topologically associating domains (TADs) and between chromatin and the nuclear lamina organize and position chromos...
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Epigenetic modulation of a hardwired 3D chromatin landscape in two naive states of pluripotency.
Published: May, 2019

Abstract: The mechanisms underlying enhancer activation and the extent to which enhancer-promoter rewiring contributes to spatiotemporal gene expression are not well understood. Using integrative and time-resolved analyses we show that the extensive transcr...
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Bromodomain inhibition of the coactivators CBP/EP300 facilitate cellular reprogramming.
Published: May, 2019

Abstract: Silencing of the somatic cell type-specific genes is a critical yet poorly understood step in reprogramming. To uncover pathways that maintain cell identity, we performed a reprogramming screen using inhibitors of chromatin factors. Here, we ident...
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ChIP-seq of plasma cell-free nucleosomes identifies cell-of-origin geneexpression programs
Published: May, 2019

Abstract: Blood cell-free DNA (cfDNA) is derived from fragmented chromatin in dying cells. As such, it remains associated with histones that may retain the covalent modifications present in the cell of origin. Until now this rich epigenetic information carr...
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Canonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing.
Published: April, 2019

Abstract: Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression i...
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PML modulates H3.3 targeting to telomeric and centromeric repeats in mouse fibroblasts.
Published: April, 2019

Abstract: Targeted deposition of histone variant H3.3 into chromatin is paramount for proper regulation of chromatin integrity, particularly in heterochromatic regions including repeats. We have recently shown that the promyelocytic leukemia (PML) protein p...
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Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development.
Published: April, 2019

Abstract: Studies in vertebrates have outlined conserved molecular control of definitive endoderm (END) development. However, recent work also shows that key molecular aspects of human END regulation differ even from rodents. Differentiation of human embryo...
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Long intergenic non-coding RNAs regulate human lung fibroblast function: Implications for idiopathic pulmonary fibrosis.
Published: April, 2019

Abstract: Phenotypic changes in lung fibroblasts are believed to contribute to the development of Idiopathic Pulmonary Fibrosis (IPF), a progressive and fatal lung disease. Long intergenic non-coding RNAs (lincRNAs) have been identified as novel regulators ...
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Defining UHRF1 Domains that Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties.
Published: April, 2019

Abstract: UHRF1 facilitates the establishment and maintenance of DNA methylation patterns in mammalian cells. The establishment domains are defined, including E3 ligase function, but the maintenance domains are poorly characterized. Here, we demonstrate tha...
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TET3 prevents terminal differentiation of adult NSCs by a non-catalytic action at Snrpn.
Published: April, 2019

Abstract: Ten-eleven-translocation (TET) proteins catalyze DNA hydroxylation, playing an important role in demethylation of DNA in mammals. Remarkably, although hydroxymethylation levels are high in the mouse brain, the potential role of TET proteins in adu...
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Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity.
Published: April, 2019

Abstract: The Polycomb repressive complexes PRC1 and PRC2 act non-redundantly at target genes to maintain transcriptional programs and ensure cellular identity. PRC2 methylates lysine 27 on histone H3 (H3K27me), while PRC1 mono-ubiquitinates histone H2A at ...
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Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies.
Published: April, 2019

Abstract: Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically ...
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Tricarboxylic Acid Cycle Activity and Remodeling of Glycerophosphocholine Lipids Support Cytokine Induction in Response to Fungal Patterns.
Published: April, 2019

Abstract: Increased glycolysis parallels immune cell activation, but the role of pyruvate remains largely unexplored. We found that stimulation of dendritic cells with the fungal surrogate zymosan causes decreases of pyruvate, citrate, itaconate, and &alpha...
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Identification of ADGRE5 as discriminating MYC target between Burkitt lymphoma and diffuse large B-cell lymphoma.
Published: April, 2019

Abstract: BACKGROUND: MYC is a heterogeneously expressed transcription factor that plays a multifunctional role in many biological processes such as cell proliferation and differentiation. It is also associated with many types of cancer including the malign...
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The FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma.
Published: April, 2019

Abstract: Frizzled family receptor 7 (FZD7), a Wnt signaling receptor, is associated with the maintenance of stem cell properties and cancer progression. FZD7 has emerged as a potential therapeutic target because it is capable of transducing both canonical ...
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Modulation of Gene Silencing by Cdc7p via H4 K16 Acetylation and Phosphorylation of Chromatin Assembly Factor CAF-1 in .
Published: April, 2019

Abstract: CAF-1 is an evolutionarily conserved H3/H4 histone chaperone that plays a key role in replication-coupled chromatin assembly and is targeted to the replication fork via interactions with PCNA, which, if disrupted, leads to epigenetic defects. In ,...
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Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.
Published: April, 2019

Abstract: The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeuti...
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Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs.
Published: March, 2019

Abstract: Expansion of transposable elements (TEs) coincides with evolutionary shifts in gene expression. TEs frequently harbor binding sites for transcriptional regulators, thus enabling coordinated genome-wide activation of species- and context-specific g...
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Point mutations in the PDX1 transactivation domain impair human β-cell development and function.
Published: March, 2019

Abstract: OBJECTIVE: Hundreds of missense mutations in the coding region of PDX1 exist; however, if these mutations predispose to diabetes mellitus is unknown. METHODS: In this study, we screened a large cohort of subjects with increased risk for diabetes a...
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ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer.
Published: March, 2019

Abstract: Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, of...
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Increased Serine and One-Carbon Pathway Metabolism by PKCλ/ι Deficiency Promotes Neuroendocrine Prostate Cancer.
Published: March, 2019

Abstract: Increasingly effective therapies targeting the androgen receptor have paradoxically promoted the incidence of neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), for which there is no effec...
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A critical regulator of Bcl2 revealed by systematic transcript discovery of lncRNAs associated with T-cell differentiation.
Published: March, 2019

Abstract: Normal T-cell differentiation requires a complex regulatory network which supports a series of maturation steps, including lineage commitment, T-cell receptor (TCR) gene rearrangement, and thymic positive and negative selection. However, the under...
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Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA.
Published: March, 2019

Abstract: Developing and adult tissues use different cis-regulatory elements. Although DNA at some decommissioned embryonic enhancers is hypomethylated in adult cells, it is unknown whether this putative epigenetic memory is complete and recoverable. We fin...
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The role of TCF3 as potential master regulator in blastemal Wilms tumors.
Published: March, 2019

Abstract: Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk...
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lncRNA KHPS1 Activates a Poised Enhancer by Triplex-Dependent Recruitment of Epigenomic Regulators.
Published: March, 2019

Abstract: Transcription of the proto-oncogene SPHK1 is regulated by KHPS1, an antisense RNA that activates SPHK1 expression by forming a triple-helical RNA-DNA-DNA structure at the SPHK1 enhancer. Triplex-mediated tethering of KHPS1 to its target gene is re...
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R-Loops Enhance Polycomb Repression at a Subset of Developmental Regulator Genes.
Published: March, 2019

Abstract: R-loops are three-stranded nucleic acid structures that form during transcription, especially over unmethylated CpG-rich promoters of active genes. In mouse embryonic stem cells (mESCs), CpG-rich developmental regulator genes are repressed by the ...
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Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology.
Published: March, 2019

Abstract: BACKGROUND: Natural killer T (NKT) cells express a T-cell receptor that recognizes endogenous and environmental glycolipid antigens. Several subsets of NKT cells have been identified, including IFN-γ-producing NKT1 cells, IL-4-producing NKT2...
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The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.
Published: March, 2019

Abstract: The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify po...
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H3K27me3 is an epigenetic barrier while KDM6A overexpression improves nuclear reprogramming efficiency.
Published: March, 2019

Abstract: Aberrant epigenetic reprogramming is a major factor of developmental failure of cloned embryos. Histone H3 lysine 27 trimethylation (H3K27me3), a histone mark for transcriptional repression, plays important roles in mammalian embryonic development...
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Genomewide analysis of 6-methyladenine DNA in peripheral blood mononuclear cells of systemic lupus erythematosus.
Published: March, 2019

Abstract: AIM: The aim of this paper is to explore the expression of 6-methyladenine (6mA) DNA and to elucidate its gene regulation role in systemic lupus erythematosus (SLE). METHODS: Twenty SLE patients and 20 normal control healthy individuals (HCs) were...
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Environmental Toxicant Induced Epigenetic Transgenerational Inheritance of Prostate Pathology and Stromal-Epithelial Cell Epigenome and Transcriptome Alterations: Ancestral Origins of Prostate Disease.
Published: February, 2019

Abstract: Prostate diseases include prostate cancer, which is the second most common male neoplasia, and benign prostatic hyperplasia (BPH), which affects approximately 50% of men. The incidence of prostate disease is increasing, and some of this increase m...
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CBX7 Induces Self-Renewal of Human Normal and Malignant Hematopoietic Stem and Progenitor Cells by Canonical and Non-canonical Interactions.
Published: February, 2019

Abstract: In this study, we demonstrate that, among all five CBX Polycomb proteins, only CBX7 possesses the ability to control self-renewal of human hematopoietic stem and progenitor cells (HSPCs). Xenotransplantation of CBX7-overexpressing HSPCs resulted i...
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Release of Immunomodulatory Ebola Virus Glycoprotein-Containing Microvesicles Is Suppressed by Tetherin in a Species-Specific Manner.
Published: February, 2019

Abstract: The Ebola virus glycoprotein (EBOV-GP) forms GP-containing microvesicles, so-called virosomes, which are secreted from GP-expressing cells. However, determinants of GP-virosome release and their functionality are poorly understood. We characterize...
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EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation.
Published: February, 2019

Abstract: Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Usin...
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A cell cycle-coordinated Polymerase II transcription compartment encompasses gene expression before global genome activation.
Published: February, 2019

Abstract: Most metazoan embryos commence development with rapid, transcriptionally silent cell divisions, with genome activation delayed until the mid-blastula transition (MBT). However, a set of genes escapes global repression and gets activated before MBT...
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Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer.
Published: January, 2019

Abstract: DNA replication timing is known to facilitate the establishment of the epigenome, however, the intimate connection between replication timing and changes to the genome and epigenome in cancer remain largely uncharacterised. Here, we perform Repli-...
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Chromatin-Based Classification of Genetically Heterogeneous AMLs into Two Distinct Subtypes with Diverse Stemness Phenotypes.
Published: January, 2019

Abstract: Global investigation of histone marks in acute myeloid leukemia (AML) remains limited. Analyses of 38 AML samples through integrated transcriptional and chromatin mark analysis exposes 2 major subtypes. One subtype is dominated by patients with&nb...
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High-throughput ChIPmentation: freely scalable, single day ChIPseq data generation from very low cell-numbers.
Published: January, 2019

Abstract: BACKGROUND: Chromatin immunoprecipitation coupled to sequencing (ChIP-seq) is widely used to map histone modifications and transcription factor binding on a genome-wide level. RESULTS: We present high-throughput ChIPmentation (HT-ChIPmentation) th...
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Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology.
Published: January, 2019

Abstract: CD4 T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARα to repress transcription of inflammatory cytokines, but is also essential for Th-media...
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Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.
Published: January, 2019

Abstract: Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tu...
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Hyper-Editing of Cell-Cycle Regulatory and Tumor Suppressor RNA Promotes Malignant Progenitor Propagation.
Published: January, 2019

Abstract: Adenosine deaminase associated with RNA1 (ADAR1) deregulation contributes to therapeutic resistance in many malignancies. Here we show that ADAR1-induced hyper-editing in normal human hematopoietic progenitors impairs miR-26a maturation, which rep...
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The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer.
Published: January, 2019

Abstract: We identified a regulatory system that acts downstream of Wnt/β-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/β-catenin gain-of-function and Bmpr1a loss-of-functio...
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The histone methyltransferase DOT1L is required for proper DNA damage response, DNA repair, and modulates chemotherapy responsiveness.
Published: January, 2019

Abstract: BACKGROUND: Disruptor of telomeric silencing 1-like (DOT1L) is a non-SET domain containing methyltransferase known to catalyze mono-, di-, and tri-methylation of histone 3 on lysine 79 (H3K79me). DOT1L-mediated H3K79me has been implicated in chrom...
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Global distribution of DNA hydroxymethylation and DNA methylation in chronic lymphocytic leukemia.
Published: January, 2019

Abstract: BACKGROUND: Chronic lymphocytic leukemia (CLL) has been a good model system to understand the functional role of 5-methylcytosine (5-mC) in cancer progression. More recently, an oxidized form of 5-mC, 5-hydroxymethylcytosine (5-hmC) has gained lot...
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Optimization of CRISPR/Cas9 Delivery to Human Hematopoietic Stem and Progenitor Cells for Therapeutic Genomic Rearrangements.
Published: January, 2019

Abstract: Editing the β-globin locus in hematopoietic stem cells is an alternative therapeutic approach for gene therapy of β-thalassemia and sickle cell disease. Using the CRISPR/Cas9 system, we genetically modified human hematopoietic stem and p...
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Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.
Published: January, 2019

Abstract: Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence cont...
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Identification of ChIP-seq and RIME grade antibodies for Estrogen Receptor alpha.
Published: January, 2019

Abstract: Estrogen Receptor alpha (ERα) plays a major role in most breast cancers, and it is the target of endocrine therapies used in the clinic as standard of care for women with breast cancer expressing this receptor. The two methods ChIP-seq (chro...
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Transcriptome-Wide Mapping 5-Methylcytosine by mC RNA Immunoprecipitation Followed by Deep Sequencing in Plant.
Published: January, 2019

Abstract: Transcriptome-wide mapping RNA modification is crucial to understand the distribution and function of RNA modifications. Here, we describe a protocol to transcriptome-wide mapping 5-methylcytosine (mC) in plant, by a RNA immunoprecipitation follow...
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Sensitivity of pituitary gonadotropes to hyperglycemia leads to epigenetic aberrations and reduced follicle-stimulating hormone levels.
Published: December, 2018

Abstract: The connection between metabolism and reproductive function is well recognized, and we hypothesized that the pituitary gonadotropes, which produce luteinizing hormone and follicle-stimulating hormone (FSH), mediate some of the effects directly via...
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DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.
Published: December, 2018

Abstract: Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamo...
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Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.
Published: December, 2018

Abstract: Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, ...
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Plasmodium falciparum gametocyte-infected erythrocytes do not adhere to human primary erythroblasts.
Published: December, 2018

Abstract: Plasmodium falciparum gametocytes, the sexual stages responsible for malaria parasite transmission, develop in the human bone marrow parenchyma in proximity to the erythroblastic islands. Yet, mechanisms underlying gametocytes interactions with th...
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Epigenetic suppression of E-cadherin expression by Snail2 during the metastasis of colorectal cancer.
Published: December, 2018

Abstract: BACKGROUND: The transcription factor Snail2 is a repressor of E-cadherin expression during carcinogenesis; however, the specific mechanisms involved in this process in human colorectal cancer (CRC) remain largely unknown. METHOD: We checked the ex...
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SIRT7-Dependent Deacetylation of Fibrillarin Controls Histone H2A Methylation and rRNA Synthesis during the Cell Cycle.
Published: December, 2018

Abstract: Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is ace...
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Enhancers in the Peril lincRNA locus regulate distant but not local genes.
Published: December, 2018

Abstract: BACKGROUND: Recently, it has become clear that some promoters function as long-range regulators of gene expression. However, direct and quantitative assessment of enhancer activity at long intergenic noncoding RNA (lincRNA) or mRNA gene bodies has...
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Human retinoic acid-regulated CD161 regulatory T cells support wound repair in intestinal mucosa.
Published: December, 2018

Abstract: Repair of tissue damaged during inflammatory processes is key to the return of local homeostasis and restoration of epithelial integrity. Here we describe CD161 regulatory T (T) cells as a distinct, highly suppressive population of T cells that me...
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Can Mitochondrial DNA be CRISPRized: Pro and Contra.
Published: December, 2018

Abstract: Mitochondria represent a chimera of macromolecules encoded either in the organellar genome, mtDNA, or in the nuclear one. If the pathway of protein targeting to different sub-compartments of mitochondria was relatively well studied, import of smal...
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Genomic integrity of ground-state pluripotency.
Published: December, 2018

Abstract: Pluripotent cells appear to be in a transient state during early development. These cells have the capability to transition into embryonic stem cells (ESCs). It has been reported that mouse pluripotent cells cultivated in chemically defined media ...
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Developmental origins of transgenerational sperm DNA methylation epimutations following ancestral DDT exposure.
Published: November, 2018

Abstract: Epigenetic alterations in the germline can be triggered by a number of different environmental factors from diet to toxicants. These environmentally induced germline changes can promote the epigenetic transgenerational inheritance of disease and p...
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Deletion of an intronic HIF-2α binding site suppresses hypoxia-induced WT1 expression.
Published: November, 2018

Abstract: Hypoxia-inducible factors (HIFs) play a key role in the adaptation to low oxygen by interacting with hypoxia response elements (HREs) in the genome. Cellular levels of the HIF-2α transcription factor subunit influence the histopathology and ...
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Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance.
Published: November, 2018

Abstract: Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Using an experimental transplantation mouse model, we demonstrate that local macrophage activation through dectin-1 and toll-like recepto...
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Sensitive tumour detection and classification using plasma cell-free DNA methylomes.
Published: November, 2018

Abstract: The use of liquid biopsies for cancer detection and management is rapidly gaining prominence. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these method...
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Integrative Proteomic Profiling Reveals PRC2-Dependent Epigenetic Crosstalk Maintains Ground-State Pluripotency.
Published: November, 2018

Abstract: The pluripotent ground state is defined as a basal state free of epigenetic restrictions, which influence lineage specification. While naive embryonic stem cells (ESCs) can be maintained in a hypomethylated state with open chromatin when grown usi...
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RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation.
Published: November, 2018

Abstract: BACKGROUND: The cellular response to ionizing radiation involves activation of p53-dependent pathways and activation of the atypical NF-κB pathway. The crosstalk between these two transcriptional networks include (co)regulation of common gen...
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TET2 inhibits tumorigenesis of breast cancer cells by regulating caspase-4.
Published: November, 2018

Abstract: Epigenetic regulators have been shown to influence breast cancer progression. However, the detailed mechanism by which TET2 plays the suppressive role in tumorigenesis remains not completely understood. We employed RT-qPCR and westernblot to exami...
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Transcription Factors Drive Tet2-Mediated Enhancer Demethylation to Reprogram Cell Fate.
Published: November, 2018

Abstract: Here, we report DNA methylation and hydroxymethylation dynamics at nucleotide resolution using C/EBPα-enhanced reprogramming of B cells into induced pluripotent cells (iPSCs). We observed successive waves of hydroxymethylation at enhancers, ...
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Sequentially acting SOX proteins orchestrate astrocyte- and oligodendrocyte-specific gene expression.
Published: November, 2018

Abstract: SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage-specific fashion remains unknown. Here, we define glial-specific gene expression in t...
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TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer.
Published: October, 2018

Abstract: Perturbed epigenomic programs play key roles in tumorigenesis, and chromatin modulators are candidate therapeutic targets in various human cancer types. To define singular and shared dependencies on DNA and histone modifiers and transcription fact...
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SUMO Safeguards Somatic and Pluripotent Cell Identities by Enforcing Distinct Chromatin States
Published: October, 2018

Abstract: Understanding general principles that safeguard cellular identity should reveal critical insights into common mechanisms underlying specification of varied cell types. Here, we show that SUMO modification acts to stabilize cell fate in a variety o...
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Centromeres License the Mitotic Condensation of Yeast Chromosome Arms.
Published: October, 2018

Abstract: During mitosis, chromatin condensation shapes chromosomes as separate, rigid, and compact sister chromatids to facilitate their segregation. Here, we show that, unlike wild-type yeast chromosomes, non-chromosomal DNA circles and chromosomes lackin...
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Oxidative stress in sperm affects the epigenetic reprogramming in early embryonic development.
Published: October, 2018

Abstract: BACKGROUND: Reactive oxygen species (ROS)-induced oxidative stress is well known to play a major role in male infertility. Sperm are sensitive to ROS damaging effects because as male germ cells form mature sperm they progressively lose the ability...
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Promoter bivalency favors an open chromatin architecture in embryonic stem cells.
Published: October, 2018

Abstract: In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not we...
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PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.
Published: October, 2018

Abstract: Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and...
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SOX4 can redirect TGF-β-mediated SMAD3-transcriptional output in a context-dependent manner to promote tumorigenesis.
Published: October, 2018

Abstract: Expression of the transcription factor SOX4 is often elevated in human cancers, where it generally correlates with tumor-progression and poor-disease outcome. Reduction of SOX4 expression results in both diminished tumor-incidence and metastasis. ...
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Angiotensin II induced CSF1 transcription is mediated by a crosstalk between different epigenetic factors in vascular endothelial cells.
Published: October, 2018

Abstract: Endothelium-derived colony stimulating factor (CSF1) plays a key role in a range of human pathologies. Angiotensin II (Ang II) has been documented to stimulate CSF1 transcription although the underlying epigenetic mechanism remains unclear. Here w...
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Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Published: October, 2018

Abstract: The disruptor of telomeric silencing 1-like (DOT1L) mediates methylation of histone H3 at position lysine 79 (H3K79). Conditional knockout of Dot1l in mouse cerebellar granule cells (Dot1l-cKO) led to a smaller external granular layer with fewer p...
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Accurate annotation of accessible chromatin in mouse and human primordial germ cells.
Published: October, 2018

Abstract: Extensive and accurate chromatin remodeling is essential during primordial germ cell (PGC) development for the perpetuation of genetic information across generations. Here, we report that distal cis-regulatory elements (CREs) marked by DNase I-hyp...
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Differential Methylation of H3K79 Reveals DOT1L Target Genes and Function in the Cerebellum In Vivo.
Published: October, 2018

Abstract: The disruptor of telomeric silencing 1-like (DOT1L) mediates methylation of histone H3 at position lysine 79 (H3K79). Conditional knockout of Dot1l in mouse cerebellar granule cells (Dot1l-cKO) led to a smaller external granular layer with fewer p...
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SOX4 inhibits oligodendrocyte differentiation of embryonic neural stem cells in vitro by inducing Hes5 expression
Published: October, 2018

Abstract: SOX4 has been shown to promote neuronal differentiation both in the adult and embryonic neural progenitors. Ectopic SOX4 expression has also been shown to inhibit oligodendrocyte differentiation in mice, however the underlying molecular mechanisms...
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Cellular localization of the cell cycle inhibitor Cdkn1c controls growth arrest of adult skeletal muscle stem cells
Published: October, 2018

Abstract: Adult skeletal muscle maintenance and regeneration depend on efficient muscle stem cell (MuSC) functions. The mechanisms coordinating cell cycle with activation, renewal, and differentiation of MuSCs remain poorly understood. Here, we investigated...
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Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China.
Published: October, 2018

Abstract: BACKGROUND: Aberrant DNA methylation occurs frequently in cancer. The aim of this study was to identify novel methylation markers in lung cancer in Xuanwei, China, through integrated genome-wide DNA methylation and gene expression studies. METHODS...
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PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.
Published: October, 2018

Abstract: BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer develop...
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Cellular localization of the cell cycle inhibitor Cdkn1c controls growth arrest of adult skeletal muscle stem cells
Published: October, 2018

Abstract: Adult skeletal muscle maintenance and regeneration depend on efficient muscle stem cell (MuSC) functions. The mechanisms coordinating cell cycle with activation, renewal, and differentiation of MuSCs remain poorly understood. Here, we investigated...
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Suppression of AMPK/aak-2 by NRF2/SKN-1 down-regulates autophagy during prolonged oxidative stress.
Published: October, 2018

Abstract: NF-E2-related factor 2 (NRF2) transcription factor has a fundamental role in cell homeostasis maintenance as one of the master regulators of oxidative and electrophilic stress responses. Previous studies have shown that a regulatory connection exi...
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The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity
Published: October, 2018

Abstract: Sepsis involves simultaneous hyperactivation of the immune system and immune paralysis, leading to both organ dysfunction and increased susceptibility to secondary infections. Acute activation of myeloid cells induced itaconate synthesis, which su...
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Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids.
Published: October, 2018

Abstract: The emergence of multiple axes is an essential element in the establishment of the mammalian body plan. This process takes place shortly after implantation of the embryo within the uterus and relies on the activity of gene regulatory networks that...
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Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo.
Published: September, 2018

Abstract: Connexins are the primary components of gap junctions, providing direct links between cells under many physiological processes. Here, we demonstrate that in addition to this canonical role, Connexins act as transcriptional regulators. We show that...
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Histone variant H2A.Z deposition and acetylation directs the canonical Notch signaling response.
Published: September, 2018

Abstract: A fundamental as yet incompletely understood feature of Notch signal transduction is a transcriptional shift from repression to activation that depends on chromatin regulation mediated by transcription factor RBP-J and associated cofactors. Incorp...
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UCP1 transrepression in Brown Fat in vivo and mineralocorticoid receptor anti-thermogenic effects.
Published: September, 2018

Abstract: OBJECTIVES: The mineralocorticoid receptor (MR), a hormone-activated transcription factor, besides its role in controlling hydroelectrolytic homeostasis, exerts pro-adipogenic and anti-thermogenic effects, inhibiting mitochondrial-uncoupling prote...
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Adenovirus E1A Activation Domain Regulates H3 Acetylation Affecting Varied Steps in Transcription at Different Viral Promoters.
Published: September, 2018

Abstract: How histone acetylation promotes transcription is not clearly understood. Here, we confirm an interaction between p300 and the adenovirus 2 large E1A activation domain (AD) and map the interacting regions in E1A by observing colocalization at an i...
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Impact of human sepsis on CCCTC-binding factor associated monocyte transcriptional response of Major Histocompatibility Complex II components.
Published: September, 2018

Abstract: BACKGROUND: Antigen presentation on monocyte surface to T-cells by Major Histocompatibility Complex, Class II (MHC-II) molecules is fundamental for pathogen recognition and efficient host response. Accordingly, loss of Major Histocompatibility Com...
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MIWI2 targets RNAs transcribed from piRNA-dependent regions to drive DNA methylation in mouse prospermatogonia.
Published: September, 2018

Abstract: Argonaute/Piwi proteins can regulate gene expression via RNA degradation and translational regulation using small RNAs as guides. They also promote the establishment of suppressive epigenetic marks on repeat sequences in diverse organisms. In mice...
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Mapping molecular landmarks of human skeletal ontogeny and pluripotent stem cell-derived articular chondrocytes.
Published: September, 2018

Abstract: Tissue-specific gene expression defines cellular identity and function, but knowledge of early human development is limited, hampering application of cell-based therapies. Here we profiled 5 distinct cell types at a single fetal stage, as well as ...
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Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development.
Published: September, 2018

Abstract: Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), although the live birth rate is relatively low. Recent studies have identified H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT...
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mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors.
Published: September, 2018

Abstract: In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs ...
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Transcription Elongation Can Affect Genome 3D Structure.
Published: September, 2018

Abstract: How transcription affects genome 3D organization is not well understood. We found that during influenza A (IAV) infection, rampant transcription rapidly reorganizes host cell chromatin interactions. These changes occur at the ends of highly transc...
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RNA Sequencing and Pathway Analysis Identify Important Pathways Involved in Hypertrichosis and Intellectual Disability in Patients with Wiedemann-Steiner Syndrome.
Published: September, 2018

Abstract: A growing number of histone modifiers are involved in human neurodevelopmental disorders, suggesting that proper regulation of chromatin state is essential for the development of the central nervous system. Among them, heterozygous de novo variant...
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Polycomb repressive complex 1 shapes the nucleosome landscape but not accessibility at target genes.
Published: August, 2018

Abstract: Polycomb group (PcG) proteins are transcriptional repressors that play important roles in regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin to limit the activity ...
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Progenitor Hyperpolarization Regulates the Sequential Generation of Neuronal Subtypes in the Developing Neocortex.
Published: August, 2018

Abstract: During corticogenesis, ventricular zone progenitors sequentially generate distinct subtypes of neurons, accounting for the diversity of neocortical cells and the circuits they form. While activity-dependent processes are critical for the different...
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Nuclear Receptor Nur77 Limits the Macrophage Inflammatory Response through Transcriptional Reprogramming of Mitochondrial Metabolism.
Published: August, 2018

Abstract: Activation of macrophages by inflammatory stimuli induces reprogramming of mitochondrial metabolism to support the production of pro-inflammatory cytokines and nitric oxide. Hallmarks of this metabolic rewiring are downregulation of α-ketogl...
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Loss of SETDB1 decompacts the inactive X chromosome in part through reactivation of an enhancer in the IL1RAPL1 gene.
Published: August, 2018

Abstract: BACKGROUND: The product of dosage compensation in female mammals is the inactive X chromosome (Xi). Xi facultative heterochromatin is organized into two different types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3). Th...
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The Alzheimer's disease-associated TREM2 gene is regulated by p53 tumor suppressor protein.
Published: August, 2018

Abstract: TREM2 mutations evoke neurodegenerative disorders, and recently genetic variants of this gene were correlated to increased risk of Alzheimer's disease. The signaling cascade originating from the TREM2 membrane receptor includes its binding partner...
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The Arabidopsis LDL1/2-HDA6 histone modification complex is functionally associated with CCA1/LHY in regulation of circadian clock genes.
Published: August, 2018

Abstract: In Arabidopsis, the circadian clock central oscillator genes are important cellular components to generate and maintain circadian rhythms. There is a negative feedback loop between the morning expressed CCA1 (CIRCADIAN CLOCK ASSOCIATED 1)/LHY (LAT...
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Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids.
Published: August, 2018

Abstract: Distinct transcriptional states are maintained through organization of chromatin, resulting from the sum of numerous repressive and active histone modifications, into tightly packaged heterochromatin versus more accessible euchromatin. Polycomb re...
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Novel dual regulators of Pseudomonas aeruginosa essential for productive biofilms and virulence.
Published: August, 2018

Abstract: Gene regulation network in Pseudomonas aeruginosa is complex. With a relatively large genome (6.2 Mb), there is a significant portion of genes that are proven or predicted to be transcriptional regulators. Many of these regulators have been shown ...
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Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability.
Published: August, 2018

Abstract: Histone H3 lysine 9 methylation (H3K9me) mediates heterochromatic gene silencing and is important for genome stability and the regulation of gene expression. The establishment and epigenetic maintenance of heterochromatin involve the recruitment o...
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HIV-2/SIV viral protein X counteracts HUSH repressor complex.
Published: August, 2018

Abstract: To evade host immune defences, human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) have evolved auxiliary proteins that target cell restriction factors. Viral protein X (Vpx) from the HIV-2/SIVsmm lineage enhances viral infection by antagoniz...
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Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.
Published: August, 2018

Abstract: Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional an...
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The transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer.
Published: July, 2018

Abstract: Syndecan 1 (SDC-1) is a cell surface proteoglycan with a significant role in cell adhesion, maintaining epithelial integrity. SDC1 expression is inversely related to aggressiveness in prostate cancer (PCa). During epithelial to mesenchymal transit...
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MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding.
Published: July, 2018

Abstract: ABSTACT: Polycomb-mediated repression of gene expression is essential for development, with a pivotal role played by trimethylation of histone H3 lysine 27 (H3K27me3), which is deposited by Polycomb Repressive Complex 2 (PRC2). The mechanism by wh...
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TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons
Published: July, 2018

Abstract: Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. We have previously shown that Tspyl2 knockout mice had impaired learning and sensorimotor gating, and TSPYL2 facilitates ...
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Forskolin Sensitizes Human Acute Myeloid Leukemia Cells to H3K27me2/3 Demethylases GSKJ4 Inhibitor via Protein Kinase A.
Published: July, 2018

Abstract: Acute myeloid leukemia (AML) is an aggressive hematological malignancy occurring very often in older adults, with poor prognosis depending on both rapid disease progression and drug resistance occurrence. Therefore, new therapeutic approaches are ...
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SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human breast cancer
Published: July, 2018

Abstract: Breast cancer is the most frequently diagnosed malignancy in women worldwide. It is well established that the complexity of carcinogenesis involves profound epigenetic deregulations that contribute to the tumorigenesis process. Deregulated H3 and ...
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A Somatically Acquired Enhancer of the Androgen Receptor Is a Noncoding Driver in Advanced Prostate Cancer.
Published: July, 2018

Abstract: Increased androgen receptor (AR) activity drives therapeutic resistance in advanced prostate cancer. The most common resistance mechanism is amplification of this locus presumably targeting the AR gene. Here, we identify and characterize a so...
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TRPM7 controls mesenchymal features of breast cancer cells by tensional regulation of SOX4.
Published: July, 2018

Abstract: Mechanically induced signaling pathways are important drivers of tumor progression. However, if and how mechanical signals affect metastasis or therapy response remains poorly understood. We previously found that the channel-kinase TRPM7, a regula...
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An Integrated and Semiautomated Microscaled Approach to Profile Cis-Regulatory Elements by Histone Modification ChIP-Seq for Large-Scale Epigenetic Studies.
Published: June, 2018

Abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) is the preferred approach to map histone modifications and identify cis-regulatory DNA elements throughout the genome. Multiple methods have been described to increase the efficiency ...
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Integrative multi-omics analysis of intestinal organoid differentiation
Published: June, 2018

Abstract: Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-e...
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Episomal HBV persistence within transcribed host nuclear chromatin compartments involves HBx.
Published: June, 2018

Abstract: BACKGROUND: In hepatocyte nuclei, hepatitis B virus (HBV) genomes occur episomally as covalently closed circular DNA (cccDNA). The HBV X protein (HBx) is required to initiate and maintain HBV replication. The functional nuclear localization of ccc...
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Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation.
Published: June, 2018

Abstract: Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recogniz...
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A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes.
Published: June, 2018

Abstract: Understanding the dynamics of endogenous protein-protein interactions in complex networks is pivotal in deciphering disease mechanisms. To enable the in-depth analysis of protein interactions in chromatin-associated protein complexes, we have prev...
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Modulation of vitamin D signaling by the pioneer factor CEBPA.
Published: June, 2018

Abstract: The myeloid master regulator CCAAT enhancer-binding protein alpha (CEBPA) is known as a pioneer factor. In this study, we report the CEBPA cistrome of THP-1 human monocytes after stimulation with the vitamin D receptor (VDR) ligand 1α,25-dih...
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The SS18-SSX Fusion Oncoprotein Hijacks BAF Complex Targeting and Function to Drive Synovial Sarcoma.
Published: June, 2018

Abstract: Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 subunit assembly. Here we demonstrate that SS18-SSX gl...
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Cyclin G and the Polycomb Repressive complexes PRC1 and PR-DUB cooperate for developmental stability
Published: June, 2018

Abstract: In Drosophila, ubiquitous expression of a short Cyclin G isoform generates extreme developmental noise estimated by fluctuating asymmetry (FA), providing a model to tackle developmental stability. This transcriptional cyclin interacts with chromat...
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Determination of the presence of 5-methylcytosine in Paramecium tetraurelia.
Published: June, 2018

Abstract: 5-methylcytosine DNA methylation regulates gene expression and developmental programming in a broad range of eukaryotes. However, its presence and potential roles in ciliates, complex single-celled eukaryotes with germline-somatic genome specializ...
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SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub.
Published: June, 2018

Abstract: SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel-Giedion syndrome. Here we show that SETBP1 binds to gDNA in AT-rich promot...
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The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.
Published: June, 2018

Abstract: To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromati...
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Immunity drives regulation in cancer through NF-κB.
Published: June, 2018

Abstract: Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breas...
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Immunity drives TET1 regulation in cancer through NF-kB
Published: June, 2018

Abstract: Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breas...
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The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia
Published: June, 2018

Abstract: Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape...
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Epigenetic regulation of vascular NADPH oxidase expression and reactive oxygen species production by histone deacetylase-dependent mechanisms in experimental diabetes.
Published: June, 2018

Abstract: Reactive oxygen species (ROS) generated by up-regulated NADPH oxidase (Nox) contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of ge...
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Increased H3K9 methylation and impaired expression of Protocadherins are associated with the cognitive dysfunctions of the Kleefstra syndrome.
Published: June, 2018

Abstract: Kleefstra syndrome, a disease with intellectual disability, autism spectrum disorders and other developmental defects is caused in humans by haploinsufficiency of EHMT1. Although EHMT1 and its paralog EHMT2 were shown to be histone methyltransfera...
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Histone H3 lysine 36 methyltransferase mobilizes NER factors to regulate tolerance against alkylation damage in fission yeast.
Published: June, 2018

Abstract: The Set2 methyltransferase and its target, histone H3 lysine 36 (H3K36), affect chromatin architecture during the transcription and repair of DNA double-stranded breaks. Set2 also confers resistance against the alkylating agent, methyl methanesulf...
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UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs.
Published: June, 2018

Abstract: The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its cata...
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Estrogen receptor α dependent regulation of estrogen related receptor β and its role in cell cycle in breast cancer.
Published: May, 2018

Abstract: BACKGROUND: Breast cancer (BC) is highly heterogeneous with ~ 60-70% of estrogen receptor positive BC patient's response to anti-hormone therapy. Estrogen receptors (ERs) play an important role in breast cancer progression and treatment. Es...
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The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity.
Published: May, 2018

Abstract: Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we i...
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Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.
Published: May, 2018

Abstract: The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix. Although Notch and other signalling pathways have...
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Polycomb Repressive Complex 2 attenuates the very high expression of the Arabidopsis gene NRT2.1.
Published: May, 2018

Abstract: PRC2 is a major regulator of gene expression in eukaryotes. It catalyzes the repressive chromatin mark H3K27me3, which leads to very low expression of target genes. NRT2.1, which encodes a key root nitrate transporter in Arabidopsis, is targeted b...
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HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types.
Published: May, 2018

Abstract: Processes like cellular senescence are characterized by complex events giving rise to heterogeneous cell populations. However, the early molecular events driving this cascade remain elusive. We hypothesized that senescence entry is triggered by an...
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Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes.
Published: May, 2018

Abstract: Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform mul...
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Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation.
Published: May, 2018

Abstract: GATA-binding protein 3 (GATA3) acts as the master transcription factor for type 2 T helper (Th2) cell differentiation and function. However, it is still elusive how GATA3 function is precisely regulated in Th2 cells. Here, we show that the transcr...
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A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.
Published: May, 2018

Abstract: Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown ...
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The Ftx Noncoding Locus Controls X Chromosome Inactivation Independently of Its RNA Products.
Published: May, 2018

Abstract: Accumulation of the Xist long noncoding RNA (lncRNA) on one X chromosome is the trigger for X chromosome inactivation (XCI) in female mammals. Xist expression, which needs to be tightly controlled, involves a cis-acting region, the X-inactiva...
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The novel BET bromodomain inhibitor BI 894999 represses super-enhancer-associated transcription and synergizes with CDK9 inhibition in AML.
Published: May, 2018

Abstract: Bromodomain and extra-terminal (BET) protein inhibitors have been reported as treatment options for acute myeloid leukemia (AML) in preclinical models and are currently being evaluated in clinical trials. This work presents a novel potent and sele...
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A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.
Published: April, 2018

Abstract: Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neuroge...
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Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.
Published: April, 2018

Abstract: Human mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limite...
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Meg3 Non-coding RNA Expression Controls Imprinting by Preventing Transcriptional Upregulation in cis.
Published: April, 2018

Abstract: Although many long non-coding RNAs (lncRNAs) are imprinted, their roles often remain unknown. The Dlk1-Dio3 domain expresses the lncRNA Meg3 and multiple microRNAs and small nucleolar RNAs (snoRNAs) on the maternal chromosome and constitutes an ep...
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Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.
Published: April, 2018

Abstract: The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylatio...
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Structural and mechanistic insights into UHRF1-mediated DNMT1 activation in the maintenance DNA methylation.
Published: April, 2018

Abstract: UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or Lys23, which is...
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A CLK3-HMGA2 Alternative Splicing Axis Impacts Human Hematopoietic Stem Cell Molecular Identity throughout Development.
Published: April, 2018

Abstract: While gene expression dynamics have been extensively cataloged during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptio...
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Epigenetics and early domestication: differences in hypothalamic DNA methylation between red junglefowl divergently selected for high or low fear of humans.
Published: April, 2018

Abstract: BACKGROUND: Domestication of animals leads to large phenotypic alterations within a short evolutionary time-period. Such alterations are caused by genomic variations, yet the prevalence of modified traits is higher than expected if they were cause...
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Comparative Analysis of Immune Cells Reveals a Conserved Regulatory Lexicon.
Published: March, 2018

Abstract: Most well-characterized enhancers are deeply conserved. In contrast, genome-wide comparative studies of steady-state systems showed that only a small fraction of active enhancers are conserved. To better understand conservation of enhancer activit...
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A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
Published: March, 2018

Abstract: Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mos...
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Epigenetic modifiers promote mitochondrial biogenesis and oxidative metabolism leading to enhanced differentiation of neuroprogenitor cells.
Published: March, 2018

Abstract: During neural development, epigenetic modulation of chromatin acetylation is part of a dynamic, sequential and critical process to steer the fate of multipotent neural progenitors toward a specific lineage. Pan-HDAC inhibitors (HDCis) trigger neur...
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Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos.
Published: March, 2018

Abstract: Copper contamination is widespread along coastal areas and exerts adverse effects on marine organisms such as mollusks. In the Pacific oyster, copper induces severe developmental abnormalities during early life stages; however, the underlying mole...
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Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Published: March, 2018

Abstract: OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the...
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PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.
Published: March, 2018

Abstract: The programmed formation of hundreds of DNA double-strand breaks (DSBs) is essential for proper meiosis and fertility. In mice and humans, the location of these breaks is determined by the meiosis-specific protein PRDM9, through the DNA-binding sp...
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The transcription factors Runx3 and ThPOK cross-regulate acquisition of cytotoxic function by human Th1 lymphocytes.
Published: February, 2018

Abstract: Cytotoxic CD4 (CD4) T cells are emerging as an important component of antiviral and antitumor immunity, but the molecular basis of their development remains poorly understood. In the context of human cytomegalovirus infection, a significant propor...
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The CUE1 domain of the SNF2-like chromatin remodeler SMARCAD1 mediates its association with KRAB-associated protein 1 (KAP1) and KAP1 target genes.
Published: February, 2018

Abstract: Chromatin in embryonic stem cells (ESCs) differs markedly from that in somatic cells, with ESCs exhibiting a more open chromatin configuration. Accordingly, ATP-dependent chromatin remodeling complexes are important regulators of ESC homeostasis. ...
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Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis.
Published: February, 2018

Abstract: Urothelial carcinoma (UC), the most common cancer of the urinary bladder causes severe morbidity and mortality, e.g. about 40.000 deaths in the EU annually, and incurs considerable costs for the health system due to the need for prolonged treatmen...
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A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response.
Published: February, 2018

Abstract: MLL/SET methyltransferases catalyze methylation of histone 3 lysine 4 and play critical roles in development and cancer. We assessed MLL/SET proteins and found that SETD1A is required for survival of acute myeloid leukemia (AML) cells. Mutagenesis...
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Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors.
Published: February, 2018

Abstract: Lympho-myeloid restricted early thymic progenitors (ETPs) are postulated to be the cell of origin for ETP leukemias, a therapy-resistant leukemia associated with frequent co-occurrence of EZH2 and RUNX1 inactivating mutations, and constitutively a...
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Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.
Published: February, 2018

Abstract: Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER) breast cancers. We investigated the chromatin recruitment, transcriptional network,...
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Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia
Published: February, 2018

Abstract: Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-1...
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Inhibition of Methyltransferase Setd7 Allows the In Vitro Expansion of Myogenic Stem Cells with Improved Therapeutic Potential.
Published: February, 2018

Abstract: The development of cell therapy for repairing damaged or diseased skeletal muscle has been hindered by the inability to significantly expand immature, transplantable myogenic stem cells (MuSCs) in culture. To overcome this limitation, a deepe...
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Miz1 Controls Schwann Cell Proliferation via H3K36me2 Demethylase Kdm8 to Prevent Peripheral Nerve Demyelination
Published: January, 2018

Abstract: Schwann cell differentiation and myelination depends on chromatin remodeling, histone acetylation, and methylation, which all affect Schwann cell proliferation. We previously reported that the deletion of the POZ (POxvirus and Zinc finger) domain ...
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Metabolic Induction of Trained Immunity through the Mevalonate Pathway.
Published: January, 2018

Abstract: Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that act...
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BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity.
Published: January, 2018

Abstract: The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge st...
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Senescence-associated reprogramming promotes cancer stemness.
Published: January, 2018

Abstract: Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysi...
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STAT5BN642H is a driver mutation for T cell neoplasia
Published: January, 2018

Abstract: STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that express...
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Genome-wide analysis of day/night DNA methylation differences in Populus nigra.
Published: January, 2018

Abstract: DNA methylation is an important mechanism of epigenetic modification. Methylation changes during stress responses and developmental processes have been well studied; however, their role in plant adaptation to the day/night cycle is poorly understo...
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Obligatory and facilitative allelic variation in the DNA methylome within common disease-associated loci
Published: January, 2018

Abstract: Integrating epigenetic data with genome-wide association study (GWAS) results can reveal disease mechanisms. The genome sequence itself also shapes the epigenome, with CpG density and transcription factor binding sites (TFBSs) strongly e...
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MLL2 conveys transcription-independent H3K4 trimethylation in oocytes
Published: January, 2018

Abstract: Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyt...
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RNA-Based dCas9–VP64 System Improves the Viability of Cryopreserved Mammalian Cells
Published: January, 2018

Abstract: Regenerative therapies require availability of an abundant healthy cell source which can be achieved by e±cient cryopreservation techniques. Here, we established a novel approach for improved cell cryopreservation using an mRNA-based dCas9-...
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Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufiency.
Published: January, 2018

Abstract: Two of the most prevalent ovarian diseases affecting women's fertility and health are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS). Previous studies have shown that exposure to a number of environmental toxicants can ...
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Cancer cell specific inhibition of Wnt/β-catenin signaling by forced intracellular acidification.
Published: January, 2018

Abstract: Use of the diabetes type II drug Metformin is associated with a moderately lowered risk of cancer incidence in numerous tumor entities. Studying the molecular changes associated with the tumor-suppressive action of Metformin we found that the onco...
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Neonatal exposure to hyperoxia leads to persistent disturbances in pulmonary histone signatures associated with NOS3 and STAT3 in a mouse model.
Published: January, 2018

Abstract: Background: Early pulmonary oxygen exposure is one of the most important factors implicated in the development of bronchopulmonary dysplasia (BPD). Methods: Here, we analyzed short- and long-term effects of neonatal hyperoxia on NOS3 and STAT3 exp...
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Analysis of DNA methylome and transcriptome profiling following Gibberellin A3 (GA3) foliar application in Nicotiana tabacum L.
Published: January, 2018

Abstract: The present work investigated a comprehensive genome-wide landscape of DNA methylome and its relationship with transcriptome upon gibberellin A3 (GA3) foliar application under practical field conditions in solanaceae model, Nicotiana tabacum L. Me...
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BRACHYURY directs histone acetylation to target loci during mesoderm development.
Published: January, 2018

Abstract: T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (...
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(Po)STAC (Polycistronic SunTAg modified CRISPR) enables live-cell and fixed-cell super-resolution imaging of multiple genes
Published: December, 2017

Abstract: CRISPR/dCas9-based labeling has allowed direct visualization of genomic regions in living cells. However, poor labeling efficiency and signal-to-background ratio have limited its application to visualize genome organization using super-resolution ...
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Cockayne's Syndrome A and B Proteins Regulate Transcription Arrest after Genotoxic Stress by Promoting ATF3 Degradation
Published: December, 2017

Abstract: Cockayne syndrome (CS) is caused by mutations in CSA and CSB. The CSA and CSB proteins have been linked to both promoting transcription-coupled repair and restoring transcription following DNA damage. We show that UV stress arrests transcription o...
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The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived neural precursor cells
Published: December, 2017

Abstract: Therapeutic intervention is an important need in ameliorating the severe consequences of Rett Syndrome (RTT), a neurological disorder caused by mutations in the X-linked gene methyl-CpG-binding protein-2 (MeCP2). Following previously observed morp...
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Oestrogen Receptor-α binds the FOXP3 promoter and modulates regulatory T-cell function in human cervical cancer
Published: December, 2017

Abstract: Oestrogen controls Foxp3 expression in regulatory T cells (Treg cells) via a mechanism thought to involve oestrogen receptor alpha (ERα), but the molecular basis and functional impact of ERα signalling in Treg cells remain unclear. We ...
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Dual SIRT1 expression patterns strongly suggests its bivalent role in human breast cancer
Published: December, 2017

Abstract: Breast cancer is the most common cancer in women, and the leading cause of cancer death in women worldwide. SIRT1 (silent mating type information regulation 2 homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation, DNA repa...
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EZH2 Histone Methyltransferase and JMJD3 Histone Demethylase Implications in Prostate Cancer
Published: December, 2017

Abstract:
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Optimization of CRISPR/Cas9 genome editing for loss-of-function in the early chick embryo
Published: December, 2017

Abstract: The advent of CRISPR/Cas9 has made genome editing possible in virtually any organism, including those not previously amenable to genetic manipulations. Here, we present an optimization of CRISPR/Cas9 for application to early avian embryos with imp...
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Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions
Published: November, 2017

Abstract: At the kilo- to megabase pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combine high-content super-resolution microscop...
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The histone code reader Spin1 controls skeletal muscle development
Published: November, 2017

Abstract: While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1M5 mice with ablation of Spin1 in myoblast precu...
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DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes
Published: November, 2017

Abstract: Storage of chromatin in restricted nuclear space requires dense packing while ensuring DNA accessibility. Thus, different layers of chromatin organization and epigenetic control mechanisms exist. Genome-wide chromatin interaction maps revealed lar...
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FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development
Published: November, 2017

Abstract: The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogen...
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In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells
Published: November, 2017

Abstract: Summary State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their in vivo state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic ...
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GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency
Published: November, 2017

Abstract: To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophobl...
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5-Methylcytosine RNA Methylation in Arabidopsis Thaliana
Published: November, 2017

Abstract: 5-Methylcytosine (m5C) is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. However, the distribution and biological functions of m5C in plant mRNAs remain lar...
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Drug-tunable multidimensional synthetic gene control using inducible degron-tagged dCas9 effectors
Published: October, 2017

Abstract: The nuclease-deactivated variant of CRISPR-Cas9 proteins (dCas9) fused to heterologous transactivation domains can act as a potent guide RNA sequence-directed inducer or repressor of gene expression in mammalian cells. In such a system the long-te...
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Alterations in the placental methylome with maternal obesity and evidence for metabolic regulation
Published: October, 2017

Abstract: The inflammatory and metabolic derangements of obesity in pregnant women generate an adverse intrauterine environment, increase pregnancy complications and adverse fetal outcomes and program the fetus for obesity and metabolic syndrome in later li...
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The Role of N-α-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting
Published: October, 2017

Abstract: Genomic imprinting is an allelic gene expression phenomenon primarily controlled by allele-specific DNA methylation at the imprinting control region (ICR), but the underlying mechanism remains largely unclear. N-α-acetyltransferase 10 protei...
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The mixed lineage leukemia 4 (MLL4) methyltransferase complex is involved in transforming growth factor beta (TGF-β)-activated gene transcription.
Published: October, 2017

Abstract: Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclea...
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Rapid Communication: The correlation between histone modifications and expression of key genes involved in accumulation of adipose tissue in the pig.
Published: October, 2017

Abstract: Histone modification is a well-known epigenetic mechanism involved in regulation of gene expression; however, it has been poorly studied in adipose tissues of the pig. Understanding the molecular background of adipose tissue development and functi...
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TET2- and TDG-mediated changes are required for the acquisition of distinct histone modifications in divergent terminal differentiation of myeloid cells
Published: September, 2017

Abstract: The plasticity of myeloid cells is illustrated by a diversity of functions including their role as effectors of innate immunity as macrophages (MACs) and bone remodelling as osteoclasts (OCs). TET2, a methylcytosine dioxygenase highly expressed in...
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Predicting stimulation-dependent enhancer-promoter interactions from ChIP-Seq time course data
Published: September, 2017

Abstract: We have developed a machine learning approach to predict stimulation-dependent enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase ...
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In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting
Published: September, 2017

Abstract: Precise genome editing involves homologous recombination between donor DNA and chromosomal sequences subjected to double-stranded DNA breaks made by programmable nucleases. Ideally, genome editing should be efficient, specific, and accurate. Howev...
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CDK8/19 Mediator kinases potentiate induction of transcription by NFκB
Published: September, 2017

Abstract: The nuclear factor-κB (NFκB) family of transcription factors has been implicated in inflammatory disorders, viral infections, and cancer. Most of the drugs that inhibit NFκB show significant side effects, possibly due to sustaine...
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Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication
Published: September, 2017

Abstract: Among other targets, the protein lysine methyltransferase PR-Set7 induces histone H4 lysine 20 monomethylation (H4K20me1), which is the substrate for further methylation by the Suv4-20h methyltransferase. Although these enzymes have been implicate...
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Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism
Published: September, 2017

Abstract: Multiple myeloma (MM) is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumor...
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DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease
Published: September, 2017

Abstract: The human genome contains ∼30,000 CpG islands (CGIs). While CGIs associated with promoters nearly always remain unmethylated, many of the ∼9,000 CGIs lying within gene bodies become methylated during development and differentiation. Both p...
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Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet
Published: September, 2017

Abstract: The circadian clock orchestrates rhythms in physiology and behavior, allowing organismal adaptation to daily environmental changes. While food intake profoundly influences diurnal rhythms in the liver, how nutritional challenges are differentially...
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A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus
Published: September, 2017

Abstract: Mutations in the Lamin A/C (LMNA) gene-encoding nuclear LMNA cause laminopathies, which include partial lipodystrophies associated with metabolic syndromes. The lipodystrophy-associated LMNA p.R482W mutation is known to impair adipogenic different...
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Chromosome contacts in activated T cells identify autoimmune disease candidate genes
Published: September, 2017

Abstract: BACKGROUND: Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4+ T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates iden...
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Epigenetic variation between urban and rural populations of Darwin's finches
Published: August, 2017

Abstract: Background The molecular basis of evolutionary change is assumed to be genetic variation. However, growing evidence suggests that epigenetic mechanisms, such as DNA methylation, may also be involved in rapid adaptation to new environments. An...
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A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation
Published: August, 2017

Abstract: Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may con...
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Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation
Published: August, 2017

Abstract: 50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lympho...
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Highly efficient gene inactivation by adenoviral CRISPR/Cas9 in human primary cells
Published: August, 2017

Abstract: Phenotypic assays using human primary cells are highly valuable tools for target discovery and validation in drug discovery. Expression knockdown (KD) of such targets in these assays allows the investigation of their role in models of disease proc...
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High Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure
Published: August, 2017

Abstract: Background -Cardiovascular disease is associated with epigenomic changes in the heart, however the endogenous structure of cardiac myocyte chromatin has never been determined. Methods -To investigate the mechanisms of epigenomic function in the he...
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Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging
Published: August, 2017

Abstract: The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and...
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Tri-methylation of H3K79 is decreased in TGF-β1-induced epithelial-to-mesenchymal transition in lung cancer
Published: August, 2017

Abstract: BACKGROUND: The epithelial-to-mesenchymal transition (EMT) enables epithelial cancer cells to acquire mesenchymal features and contributes to metastasis and resistance to treatment. This process involves epigenetic reprogramming for gene expres...
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Maternal obesity programs increased leptin gene expression in rat male offspring via epigenetic modifications in a depot-specific manner
Published: August, 2017

Abstract: OBJECTIVE: According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates predispose offspring to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly develop...
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A novel FOXA1/ESR1 interacting pathway: A study of Oncomine™ breast cancer microarrays
Published: August, 2017

Abstract: Forkhead box protein A1 (FOXA1) is essential for the growth and differentiation of breast epithelium, and has a favorable outcome in breast cancer (BC). Elevated FOXA1 expression in BC also facilitates hormone responsiveness in estrogen receptor (...
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Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation
Published: August, 2017

Abstract: Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine...
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Increased 5-hydroxymethylation levels in the hippocampus of rat extinguished from cocaine self-administration
Published: July, 2017

Abstract: Drug craving and relapse risk during abstinence from cocaine are thought to be caused by persistent changes in transcription and chromatin regulation. Although several brain regions are involved in these processes, the hippocampus seems to play an...
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Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription
Published: July, 2017

Abstract: Heterochromatic DNA domains have important roles in the regulation of gene expression and maintenance of genome stability by silencing repetitive DNA elements and transposons. From fission yeast to mammals, heterochromatin assembly at DNA repeats ...
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Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements
Published: July, 2017

Abstract: Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poo...
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Ectopic application of the repressive histone modification H3K9me2 establishes post-zygotic reproductive isolation in Arabidopsis thaliana
Published: July, 2017

Abstract: Hybrid seed lethality as a consequence of interspecies or interploidy hybridizations is a major mechanism of reproductive isolation in plants. This mechanism is manifested in the endosperm, a dosage-sensitive tissue supporting embryo growth. Dereg...
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Platelet function is modified by common sequence variation in megakaryocyte super enhancers
Published: July, 2017

Abstract: Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms ...
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Mouse models of 17q21.31 microdeletion and microduplication syndromes highlight the importance of Kansl1 for cognition
Published: July, 2017

Abstract: Koolen-de Vries syndrome (KdVS) is a multi-system disorder characterized by intellectual disability, friendly behavior, and congenital malformations. The syndrome is caused either by microdeletions in the 17q21.31 chromosomal region or by variants...
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Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b
Published: July, 2017

Abstract: Background Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances th...
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TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors
Published: July, 2017

Abstract: Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC...
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Dynamic Reorganization of Chromatin Accessibility Signatures during Dedifferentiation of Secretory Precursors into Lgr5+ Intestinal Stem Cells
Published: July, 2017

Abstract: Replicating Lgr5+ stem cells and quiescent Bmi1+ cells behave as intestinal stem cells (ISCs) in vivo. Disrupting Lgr5+ ISCs triggers epithelial renewal from Bmi1+ cells, from secretory or absorptive progenitors, and from Paneth cell precurso...
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The RNA helicase DHX9 establishes nucleolar heterochromatin, and this activity is required for embryonic stem cell differentiation
Published: July, 2017

Abstract: Long non-coding RNAs (lncRNAs) have been implicated in the regulation of chromatin conformation and epigenetic patterns. lncRNA expression levels are widely taken as an indicator for functional properties. However, the role of RNA processing in mo...
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Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways.
Published: July, 2017

Abstract: Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely compar...
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Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines
Published: June, 2017

Abstract: Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, ...
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Inhibition of Histone H3K9 Methylation by BIX-01294 Promotes Stress-Induced Microspore Totipotency and Enhances Embryogenesis Initiation
Published: June, 2017

Abstract: Microspore embryogenesis is a process of cell reprogramming, totipotency acquisition and embryogenesis initiation, induced in vitro by stress treatments and widely used in plant breeding for rapid production of doubled-haploids, but its regulating...
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Neuropeptide Y expression marks partially differentiated β cells in mice and humans
Published: June, 2017

Abstract: β Cells are formed in embryonic life by differentiation of endocrine progenitors and expand by replication during neonatal life, followed by transition into functional maturity. In this study, we addressed the potential contribution of neurop...
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DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats
Published: June, 2017

Abstract: Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigen...
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Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A
Published: June, 2017

Abstract: Background Hypericin-mediated photodynamic therapy (HY-PDT) has recently captured increased attention as an alternative minimally invasive anticancer treatment, although cancer cells may acquire resistance. Therefore, combination treatments m...
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HDAC1 links early life stress to schizophrenia-like phenotypes
Published: June, 2017

Abstract: Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate...
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ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing
Published: June, 2017

Abstract: Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specif...
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Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation
Published: May, 2017

Abstract: Monomethylation of histone H3 at lysine 4 (H3K4me1) and acetylation of histone H3 at lysine 27 (H3K27ac) are correlated with transcriptionally engaged enhancer elements, but the functional impact of these modifications on enhancer activity is ...
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Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes
Published: May, 2017

Abstract: Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species...
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RNA Polymerase III Subunit POLR3G Regulates Specific Subsets of PolyA(+) and SmallRNA Transcriptomes and Splicing in Human Pluripotent Stem Cells.
Published: May, 2017

Abstract: POLR3G is expressed at high levels in human pluripotent stem cells (hPSCs) and is required for maintenance of stem cell state through mechanisms not known in detail. To explore how POLR3G regulates stem cell state, we carried out deep-sequencing a...
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CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes
Published: May, 2017

Abstract: An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methy...
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The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis.
Published: May, 2017

Abstract: In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Altho...
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Mercury-induced epigenetic transgenerational inheritance of abnormal neurobehavior is correlated with sperm epimutations in zebrafish.
Published: May, 2017

Abstract: Methylmercury (MeHg) is a ubiquitous environmental neurotoxicant, with human exposures predominantly resulting from fish consumption. Developmental exposure of zebrafish to MeHg is known to alter their neurobehavior. The current study investigated...
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Critical threshold levels of DNA methyltransferase 1 are required to maintain DNA methylation across the genome in human cancer cells.
Published: April, 2017

Abstract: Reversing DNA methylation abnormalities and associated gene silencing, through inhibiting DNA methyltransferases (DNMTs) is an important potential cancer therapy paradigm. Maximizing this potential requires defining precisely how these enzymes mai...
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Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae
Published: April, 2017

Abstract: Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG prote...
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DNA breaks and chromatin structural changes enhance the transcription of Autoimmune Regulator target genes
Published: April, 2017

Abstract: The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic aut...
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The Role of S-Palmitoylation of the Human Glucocorticoid Receptor (hGR) in Mediating the Nongenomic Glucocorticoid Actions
Published: April, 2017

Abstract: Background: Many rapid nongenomic glucocorticoid actions are mediated by membrane-bound glucocorticoid receptors (GRs). S-palmitoylation is a lipid post-translational modification that mediates the membrane localization of some steroid receptors. ...
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Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis
Published: April, 2017

Abstract: OBJECTIVE: Aberrant activation of synovial fibroblasts (SFs) is a key determinant in the pathogenesis of rheumatoid arthritis (RA). We aimed to produce a map of gene expression and epigenetic changes occurring in this cell type during disease pro...
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H2A monoubiquitination in Arabidopsis thaliana is generally independent of LHP1 and PRC2 activity
Published: April, 2017

Abstract: BACKGROUND: Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in which PRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubi...
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Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression
Published: April, 2017

Abstract: BACKGROUND: H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression. METHODS: We investigated genome-wide H3K27me3 histone methy...
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c-Myc Antagonises the Transcriptional Activity of the Androgen Receptor in Prostate Cancer Affecting Key Gene Networks
Published: April, 2017

Abstract: Prostate cancer (PCa) is the most common non-cutaneous cancer in men. The androgen receptor (AR), a ligand-activated transcription factor, constitutes the main drug target for advanced cases of the disease. However, a variety of other transcriptio...
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Regulation of DNA demethylation by the XPC DNA repair complex in somatic and pluripotent stem cells.
Published: April, 2017

Abstract: Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent state during cellular reprogramming requires DNA methylation to silence somatic gene expression and dynamic DNA demethylation to activate pluripotency gene transcriptio...
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Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
Published: March, 2017

Abstract: A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene ...
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Microinjection of Antibodies Targeting the Lamin A/C Histone-Binding Site Blocks Mitotic Entry and Reveals Separate Chromatin Interactions with HP1, CenpB and PML.
Published: March, 2017

Abstract: Lamins form a scaffold lining the nucleus that binds chromatin and contributes to spatial genome organization; however, due to the many other functions of lamins, studies knocking out or altering the lamin polymer cannot clearly distinguish betwee...
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Trimethylation and Acetylation of β-Catenin at Lysine 49 Represent Key Elements in ESC Pluripotency
Published: March, 2017

Abstract: Wnt/β-catenin signaling is required for embryonic stem cell (ESC) pluripotency by inducing mesodermal differentiation and inhibiting neuronal differentiation; however, how β-catenin counter-regulates these differentiation pathways is unk...
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Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme
Published: March, 2017

Abstract: Mutations in chromatin modifier genes are frequently associated with neurodevelopmental diseases. We herein demonstrate that the chromodomain helicase DNA-binding protein 7 (Chd7), frequently associated with CHARGE syndrome, is indispensable for n...
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Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells
Published: March, 2017

Abstract: Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe2+-dependen...
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Decoupling of DNA methylation and activity of intergenic LINE-1 promoters in colorectal cancer
Published: March, 2017

Abstract: Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased toward young and transpositionally active elements. He...
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miR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis
Published: March, 2017

Abstract: Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in idiopathic pulmonary fibrosis (IPF) regulation is ambiguous. Our previous stud...
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ERK-Induced Activation of TCF Family of SRF Cofactors Initiates a Chromatin Modification Cascade Associated with Transcription
Published: March, 2017

Abstract: We investigated the relationship among ERK signaling, histone modifications, and transcription factor activity, focusing on the ERK-regulated ternary complex factor family of SRF partner proteins. In MEFs, activation of ERK by TPA stimulation indu...
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Connexin43 controls N-cadherin transcription during collective cell migration
Published: March, 2017

Abstract: Connexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a myster...
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Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in mice
Published: March, 2017

Abstract: Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinid...
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Krüppel-like transcription factor KLF10 suppresses TGFβ-induced epithelial-to-mesenchymal transition via a negative feedback mechanism
Published: March, 2017

Abstract: TGFβ-SMAD signaling exerts a contextual effect that suppresses malignant growth early in epithelial tumorigenesis but promotes metastasis at later stages. Longstanding challenges in resolving this functional dichotomy may uncover new strategi...
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Assessing histone demethylase inhibitors in cells: lessons learned
Published: March, 2017

Abstract: Background Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for...
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Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.
Published: February, 2017

Abstract: Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, inc...
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H3.Y discriminates between HIRA and DAXX chaperone complexes and reveals unexpected insights into human DAXX-H3.3-H4 binding and deposition requirements
Published: February, 2017

Abstract: Histone chaperones prevent promiscuous histone interactions before chromatin assembly. They guarantee faithful deposition of canonical histones and functionally specialized histone variants into chromatin in a spatial- and temporally-restricted ma...
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RNF40 regulates gene expression in an epigenetic context-dependent manner
Published: February, 2017

Abstract: BACKGROUND: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively ac...
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Jmjd2c/Kdm4c facilitates the assembly of essential enhancer-protein complexes at the onset of embryonic stem cell differentiation
Published: February, 2017

Abstract: Jmjd2 H3K9 demethylases cooperate in promoting mouse embryonic stem cell (ESC) identity. However, little is known about their importance at the exit of ESC pluripotency. Here, we reveal that Jmjd2c facilitates this process by stabilising the assem...
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Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects
Published: February, 2017

Abstract: Both Reelin (RELN) and glutamate decarboxylase 67 (GAD1) have been implicated in the pathophysiology of Autism Spectrum Disorders (ASD). We have previously shown that both mRNAs are reduced in the cerebella (CB) of ASD subjects through a mechanism...
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The non-coding variant rs1800734 enhances DCLK3 expression through long-range interaction and promotes colorectal cancer progression.
Published: February, 2017

Abstract: Genome-wide association studies have identified a great number of non-coding risk variants for colorectal cancer (CRC). To date, the majority of these variants have not been functionally studied. Identification of allele-specific transcription fac...
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Menin regulates Inhbb expression through an Akt/Ezh2-mediated H3K27 histone modification
Published: February, 2017

Abstract: Although Men1 is a well-known tumour suppressor gene, little is known about the functions of Menin, the protein it encodes for. Since few years, numerous publications support a major role of Menin in the control of epigenetics gene regulation. Whi...
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A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation
Published: February, 2017

Abstract: Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the ho...
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H3K23me1 is an evolutionarily conserved histone modification associated with CG DNA methylation in Arabidopsis
Published: February, 2017

Abstract: Amino-terminal tails of histones are targets for diverse post-translational modifications whose combinatorial action may constitute a code that will be read and interpreted by cellular proteins to define particular transcriptional states. Here, we...
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Intergenerational Transmission of Enhanced Seizure Susceptibility after Febrile Seizures
Published: February, 2017

Abstract: Environmental exposure early in development plays a role in susceptibility to disease in later life. Here, we demonstrate that prolonged febrile seizures induced by exposure of rat pups to a hyperthermic environment enhance seizure susceptibility ...
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Genome-wide analyses of four major histone modifications in Arabidopsis hybrids at the germinating seed stage
Published: February, 2017

Abstract: Background Hybrid vigour (heterosis) has been used for decades in cropping agriculture, especially in the production of maize and rice, because hybrid varieties exceed their parents in plant biomass and seed yield. The molecular basis of hybrid...
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Genomic characterization and dynamic methylation of promoter facilitates transcriptional regulation of H2A variants, H2A.1 and H2A.2 in various pathophysiological states of hepatocyte
Published: February, 2017

Abstract: Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptio...
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Suppression of RUNX1/ETO oncogenic activity by a small molecule inhibitor of tetramerization
Published: February, 2017

Abstract: RUNX1/ETO, the product of the t(8;21) chromosomal translocation, is required for the onset and maintenance of one of the most common forms of acute myeloid leukemia (AML). RUNX1/ETO has a modular structure and, besides the DN A-binding domain (Run...
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Muscle catabolic capacities and global hepatic epigenome are modified in juvenile rainbow trout fed different vitamin levels at first feeding
Published: February, 2017

Abstract: Based on the concept of nutritional programming in mammals, we tested whether a short term hyper or hypo vitamin stimulus during first-feeding could induce long-lasting changes in nutrient metabolism in rainbow trout. Trout alevins received during...
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Applying the INTACT method to purify endosperm nuclei and to generate parental-specific epigenome profiles.
Published: February, 2017

Abstract: The early endosperm tissue of dicot species is very difficult to isolate by manual dissection. This protocol details how to apply the INTACT (isolation of nuclei tagged in specific cell types) system for isolating early endosperm nuclei of Arabido...
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Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures
Published: February, 2017

Abstract: Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that includ...
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Differential DNA Methylation Regions in Adult Human Sperm following Adolescent Chemotherapy: Potential for Epigenetic Inheritance.
Published: February, 2017

Abstract: BACKGROUND: The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Previous studies have demonstrated a numb...
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DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma
Published: January, 2017

Abstract: Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genet...
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MLL-AF9 and MLL-AF4 oncofusion proteins bind a distinct enhancer repertoire and target the RUNX1 program in 11q23 acute myeloid leukemia.
Published: January, 2017

Abstract: In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF...
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Snail2 and Zeb2 repress P-Cadherin to define embryonic territories in the chick embryo
Published: January, 2017

Abstract: Snail and Zeb transcription factors induce epithelial to mesenchymal transition (EMT) in embryonic and adult tissues by direct repression of E-Cadherin transcription. The repression of E-Cadherin transcription by the EMT inducers Snail1 and Zeb2 p...
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Praja1 E3 ubiquitin ligase promotes skeletal myogenesis through degradation of EZH2 upon p38α activation
Published: January, 2017

Abstract: Polycomb proteins are critical chromatin modifiers that regulate stem cell differentiation via transcriptional repression. In skeletal muscle progenitors Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2 ...
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Differentiation of Mouse Enteric Nervous System Progenitor Cells is Controlled by Endothelin 3 and Requires Regulation of Ednrb by SOX10 and ZEB2
Published: January, 2017

Abstract: Background & Aims Maintenance and differentiation of progenitor cells in the developing enteric nervous system (ENS) are controlled by molecules such as the signaling protein endothelin 3 (EDN3), its receptor (the endothelin receptor type B...
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Rapid Recall Ability of Memory T cells is Encoded in their Epigenome
Published: January, 2017

Abstract: Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the na&i...
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Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain
Published: January, 2017

Abstract: Background Recent work has identified and mapped a range of posttranscriptional modifications in mRNA, including methylation of the N6 and N1 positions in adenine, pseudouridylation, and methylation of carbon 5 in cytosine (m5C). However, knowl...
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HMCan-diff: a method to detect changes in histone modifications in cells with different genetic characteristics
Published: January, 2017

Abstract: Comparing histone modification profiles between cancer and normal states, or across different tumor samples, can provide insights into understanding cancer initiation, progression and response to therapy. ChIP-seq histone modification data of canc...
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High resolution methylation analysis of the HoxA5 regulatory region in different somatic tissues of laboratory mouse during development
Published: January, 2017

Abstract: Homeobox genes encode a group of DNA binding regulatory proteins whose key function occurs in the spatial-temporal organization of genome during embryonic development and differentiation. The role of these Hox genes during ontogenesis makes it an ...
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Arabidopsis SWI/SNF chromatin remodeling complex binds both promoters and terminators to regulate gene expression
Published: December, 2016

Abstract: ATP-dependent chromatin remodeling complexes are important regulators of gene expression in Eukaryotes. In plants, SWI/SNF-type complexes have been shown critical for transcriptional control of key developmental processes, growth and stress respon...
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Co-occurrence of Histone H3 K27M and BRAF V600E mutations in paediatric midline grade I ganglioglioma
Published: December, 2016

Abstract: Ganglioglioma (GG) is a grade I tumour characterized by alterations in the MAPK pathway, including BRAF V600E mutation. Recently, diffuse midline glioma with an H3 K27M mutation was added to the WHO 2016 classification as a new grade IV entity. As...
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Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals
Published: December, 2016

Abstract: The functionality of stem cells declines during ageing, and this decline contributes to ageing-associated impairments in tissue regeneration and function. Alterations in developmental pathways have been associated with declines in stem-cell functi...
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Nitric oxide modulates histone acetylation at stress genes by inhibition of histone deacetylases
Published: December, 2016

Abstract: Histone acetylation, which is an important mechanism to regulate gene expression, is controlled by the opposing action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In animals, several HDACs are subjected to regulation by ...
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Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity
Published: December, 2016

Abstract: Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomi...
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FOXA1 Directs H3K4 Monomethylation at Enhancers via Recruitment of the Methyltransferase MLL3
Published: December, 2016

Abstract: FOXA1 is a pioneer factor that binds to enhancer regions that are enriched in H3K4 mono- and dimethylation (H3K4me1 and H3K4me2). We performed a FOXA1 rapid immunoprecipitation mass spectrometry of endogenous proteins (RIME) screen in ERα-po...
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Immunometabolic Pathways in BCG-Induced Trained Immunity
Published: December, 2016

Abstract: The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such ...
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A transcription factor pulse can prime chromatin for heritable transcriptional memory
Published: December, 2016

Abstract: Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in post-mitotic cells, w...
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Potent and selective bivalent inhibitors of BET bromodomains
Published: December, 2016

Abstract: Proteins of the bromodomain and extraterminal (BET) family, in particular bromodomain-containing protein 4 (BRD4), are of great interest as biological targets. BET proteins contain two separate bromodomains, and existing inhibitors bind to them mo...
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Lhx2 interacts with the NuRD complex and regulates cortical neuron subtype determinants Fezf2 and Sox11
Published: December, 2016

Abstract: n the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to differentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the p...
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ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization
Published: November, 2016

Abstract: Epigenetic, transcriptional and signaling processes in the nucleolus regulate rRNA transcription and cell growth. We report here that the tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization ...
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Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2
Published: November, 2016

Abstract: The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methy...
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Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1
Published: November, 2016

Abstract: Neural cell fate acquisition is mediated by transcription factors expressed in nascent neuroectoderm, including Geminin and members of the Zic transcription factor family. However, regulatory networks through which this occurs are not well defined...
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TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells
Published: November, 2016

Abstract: BACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable ele...
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Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
Published: November, 2016

Abstract: Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in thr...
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β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance
Published: November, 2016

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

Abstract: The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these...
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The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs
Published: November, 2016

Abstract: The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found ...
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Reader domain specificity and lysine demethylase-4 family function
Published: November, 2016

Abstract: The KDM4 histone demethylases are conserved epigenetic regulators linked to development, spermatogenesis and tumorigenesis. However, how the KDM4 family targets specific chromatin regions is largely unknown. Here, an extensive histone peptide micr...
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Enhanced CRISPR/Cas9-mediated precise genome editing by improved design and delivery of gRNA, Cas9 nuclease, and donor DNA
Published: November, 2016

Abstract: While CRISPR-based gene knock out in mammalian cells has proven to be very efficient, precise insertion of genetic elements via the cellular homology directed repair (HDR) pathway remains a rate-limiting step to seamless genome editing. Under the ...
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TET2 binds the androgen receptor and loss is associated with prostate cancer
Published: November, 2016

Abstract: Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumou...
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Chromatin Preparation and Chromatin Immuno-precipitation from Drosophila Embryos
Published: November, 2016

Abstract: This protocol provides specific details on how to perform Chromatin immunoprecipitation (ChIP) from Drosophila embryos. ChIP allows the matching of proteins or histone modifications to specific genomic regions. Formaldehyde-cross-linked chromatin ...
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Iterative Fragmentation Improves the Detection of ChIP-seq Peaks for Inactive Histone Marks
Published: October, 2016

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

Abstract: Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel-Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have a...
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Chronic stress leads to epigenetic dysregulation in the neuropeptide-Y and cannabinoid CB1 receptor genes in the mouse cingulate cortex
Published: October, 2016

Abstract: Persistent stress triggers a variety of mechanisms, which may ultimately lead to the occurrence of anxiety- and depression-related disorders. Epigenetic modifications represent a mechanism by which chronic stress mediates long-term effects. Here, ...
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Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a
Published: October, 2016

Abstract: Pluripotent embryonic stem cells (ESCs) self-renew or differentiate into all tissues of the developing embryo and cell-specification factors are necessary to balance gene expression. Here we delineate the function of the PHD-finger protein 5a (Phf...
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Neonatal monocytes exhibit a unique histone modification landscape
Published: September, 2016

Abstract: Background Neonates have dampened expression of pro-inflammatory cytokines and difficulty clearing pathogens. This makes them uniquely susceptible to infections, but the factors regulating neonatal-specific immune responses are poorly understoo...
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BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire
Published: September, 2016

Abstract: Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in ...
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Coordinate redeployment of PRC1 proteins suppresses tumor formation during Drosophila development
Published: September, 2016

Abstract: Polycomb group proteins form two main complexes, PRC2 and PRC1, which generally coregulate their target genes. Here we show that PRC1 components act as neoplastic tumor suppressors independently of PRC2 function. By mapping the distribution of PRC...
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Overexpression of histone demethylase Fbxl10 leads to enhanced migration in mouse embryonic fibroblasts.
Published: September, 2016

Abstract: Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to...
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Heterochromatic histone modifications at transposons in Xenopus tropicalis embryos
Published: September, 2016

Abstract: Transposable elements are parasitic genomic elements that can be deleterious for host gene function and genome integrity. Heterochromatic histone modifications are involved in the repression of transposons. However, it remains unknown how these hi...
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Allelic reprogramming of the histone modification H3K4me3 in early mammalian development
Published: September, 2016

Abstract: Histone modifications are fundamental epigenetic regulators that control many crucial cellular processes1. However, whether these marks can be passed on from mammalian gametes to the next generation is a long-standing question that remains unanswe...
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Detection of Protein-Protein Interactions and Posttranslational Modifications Using the Proximity Ligation Assay: Application to the Study of the SUMO Pathway.
Published: September, 2016

Abstract: The detection of protein-protein interactions by imaging techniques often requires the overexpression of the proteins of interest tagged with fluorescent molecules, which can affect their biological properties and, subsequently, flaw experiment in...
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Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition
Published: August, 2016

Abstract: Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer1. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor cl...
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Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer
Published: August, 2016

Abstract: Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program1. Somatic copy num...
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Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates.
Published: August, 2016

Abstract: The rainbow trout, a carnivorous fish, displays a ‘glucose-intolerant’ phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely...
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H3.3 demarcates GC-rich coding and subtelomeric regions and serves as potential memory mark for virulence gene expression in Plasmodium falciparum
Published: August, 2016

Abstract: Histones, by packaging and organizing the DNA into chromatin, serve as essential building blocks for eukaryotic life. The basic structure of the chromatin is established by four canonical histones (H2A, H2B, H3 and H4), while histone variants are ...
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Clinical, Imaging, Histopathological and Molecular Characterization of Anaplastic Ganglioglioma
Published: August, 2016

Abstract: Anaplastic ganglioglioma (AGG) is a rare and malignant variant of ganglioglioma. According to the World Health Organization classification version 2016, their histopathological grading criteria are still ill-defined. The aim of the present study w...
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The Development of a Viral Mediated CRISPR/Cas9 System with Doxycycline Dependent gRNA Expression for Inducible In vitro and In vivo Genome Editing.
Published: August, 2016

Abstract: The RNA-guided Cas9 nuclease, from the type II prokaryotic Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) adaptive immune system, has been adapted and utilized by scientists to edit the genomes of eukaryotic cells. Here, we re...
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reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4(+) memory T cells
Published: August, 2016

Abstract: The combinatorial action of co-localizing chromatin modifications and regulators determines chromatin structure and function. However, identifying co-localizing chromatin features in a high-throughput manner remains a technical challenge. Here we ...
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HDAC1 negatively regulates Bdnf and Pvalb required for parvalbumin interneuron maturation in an experience-dependent manner
Published: August, 2016

Abstract: During early postnatal development, neuronal circuits are sculpted by sensory experience provided by the external environment. This experience-dependent regulation of circuitry development consolidates the balance of excitatory-inhibitory (E/I) ne...
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Anti-RAINBOW dye-specific antibodies as universal tools for the visualization of prestained protein molecular weight markers in Western blot analysis
Published: August, 2016

Abstract: Western blotting is one of the most widely used techniques in molecular biology and biochemistry. Prestained proteins are used as molecular weight standards in protein electrophoresis. In the chemiluminescent Western blot analysis, however, these ...
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Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary Hotspot Gene tan in Drosophila melanogaster
Published: August, 2016

Abstract: Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotyp...
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Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming
Published: August, 2016

Abstract: Erasure of epigenetic memory is required to convert somatic cells towards pluripotency. Reactivation of the inactive X chromosome (Xi) has been used to model epigenetic reprogramming in mouse, but human studies are hampered by Xi epigenetic instab...
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MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis
Published: August, 2016

Abstract: DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF...
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Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ-mediated host defenses
Published: August, 2016

Abstract: An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In t...
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Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma
Published: August, 2016

Abstract: The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi) have shown high response rates and extended survival in patients with melanoma who bear t...
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Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress
Published: August, 2016

Abstract: Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of resveratrol remained largely controversial. Here, we demonstrate that under physiologically relevan...
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Enhancer decommissioning by Snail1-induced competitive displacement of TCF7L2 and down-regulation of transcriptional activators results in EPHB2 silencing
Published: August, 2016

Abstract: Transcriptional silencing is a major cause for the inactivation of tumor suppressor genes, however, the underlying mechanisms are only poorly understood. The EPHB2 gene encodes a receptor tyrosine kinase that controls epithelial cell migration and...
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Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription
Published: August, 2016

Abstract: Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific cont...
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Severe muscle wasting and denervation in mice lacking the RNA-binding protein ZFP106
Published: August, 2016

Abstract: Innervation of skeletal muscle by motor neurons occurs through the neuromuscular junction, a cholinergic synapse essential for normal muscle growth and function. Defects in nerve-muscle signaling cause a variety of neuromuscular disorders with fea...
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Role of CREB on heme oxygenase-1 induction in adrenal cells: involvement of the PI3K pathway
Published: August, 2016

Abstract: In addition to the well-known function of ACTH as the main regulator of adrenal steroidogenesis, we have previously demonstrated its effect on the transcriptional stimulation of HO-1 expression, a component of the cellular antioxidant defense syst...
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Epigenetic dynamics of monocyte-to-macrophage differentiation
Published: July, 2016

Abstract: BACKGROUND: Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete tran...
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Converging disease genes in ICF syndrome: ZBTB24 controls expression of CDCA7 in mammals
Published: July, 2016

Abstract: For genetically heterogeneous diseases a better understanding of how the underlying gene defects are functionally interconnected will be important for dissecting disease etiology. The Immunodeficiency, Centromeric instability, Facial anomalies (IC...
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Dnmt3a and Dnmt3b Associate with Enhancers to Regulate Human Epidermal Stem Cell Homeostasis
Published: July, 2016

Abstract: The genome-wide localization and function of endogenous Dnmt3a and Dnmt3b in adult stem cells are unknown. Here, we show that in human epidermal stem cells, the two proteins bind in a histone H3K36me3-dependent manner to the most active enhancers ...
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Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis
Published: July, 2016

Abstract: Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality wi...
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H3K4 acetylation, H3K9 acetylation and H3K27 methylation in breast tumor molecular subtypes
Published: July, 2016

Abstract: AIM: Here, we investigated how the St Gallen breast molecular subtypes displayed distinct histone H3 profiles. PATIENTS & METHODS: 192 breast tumors divided into five St Gallen molecular subtypes (luminal A, luminal B HER2-, luminal B HER...
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Combined analysis of DNA methylome and transcriptome reveal novel candidate genes with susceptibility to bovine Staphylococcus aureus subclinical mastitis
Published: July, 2016

Abstract: Subclinical mastitis is a widely spread disease of lactating cows. Its major pathogen is Staphylococcus aureus (S. aureus). In this study, we performed genome-wide integrative analysis of DNA methylation and transcriptional expression to identify ...
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5-hydroxymethylcytosine marks postmitotic neural cells in the adult and developing vertebrate central nervous system
Published: July, 2016

Abstract: The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that is abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such a mark is suggested to play key roles in...
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MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML
Published: July, 2016

Abstract: Homeobox genes are known to be key factors in leukemogenesis. Although the TALE family homeodomain factor Meis1 has been linked to malignancy, a role for MEIS2 is less clear. Here, we demonstrate that MEIS2 is expressed at high levels in patients ...
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Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family
Published: July, 2016

Abstract: Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4, and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in induced pluripotent stem cells (iPSCs) have been shown to b...
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Epigenetic silencing of serine protease HTRA1 drives polyploidy
Published: July, 2016

Abstract: BACKGROUND: Increased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, and chromosomal instability are frequently observed characteristics of cancer cells. While some aspects of these events and the checkpoint mechanisms...
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Methylation of the Sox9 and Oct4 promoters and its correlation with gene expression during testicular development in the laboratory mouse
Published: July, 2016

Abstract: Sox9 and Oct4 are two important regulatory factors involved in mammalian development. Sox9, a member of the group E Sox transcription factor family, has a crucial role in the development of the genitourinary system, while Oct4, commonly known as o...
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Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies
Published: July, 2016

Abstract: Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations i...
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The dynamic interactome and genomic targets of Polycomb complexes during stem-cell differentiation
Published: July, 2016

Abstract: Although the core subunits of Polycomb group (PcG) complexes are well characterized, little is known about the dynamics of these protein complexes during cellular differentiation. We used quantitative interaction proteomics and genome-wide profili...
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Epigenetic Modifications with DZNep, NaBu and SAHA in Luminal and Mesenchymal-like Breast Cancer Subtype Cells
Published: July, 2016

Abstract: BACKGROUND/AIM: Numerous studies have shown that breast cancer and epigenetic mechanisms have a very powerful interactive relation. The MCF7 cell line, representative of luminal subtype and the MDA-MB 231 cell line representative of mesenchymal-l...
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Genome-Wide DNA Methylation in Mixed Ancestry Individuals with Diabetes and Prediabetes from South Africa
Published: June, 2016

Abstract: Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation an...
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Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks
Published: June, 2016

Abstract: Chronic lymphocytic leukaemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, here we present genome-wide chromatin accessibil...
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Expression of the Parkinson's Disease-Associated Gene Alpha-Synuclein is Regulated by the Neuronal Cell Fate Determinant TRIM32
Published: June, 2016

Abstract: Alpha-synuclein is an abundant neuronal protein which has been associated with physiological processes like synaptic function, neurogenesis, and neuronal differentiation but also with pathological neurodegeneration. Indeed, alpha-synuclein (snca) ...
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Molecular and Epigenetic Biomarkers in Luminal Androgen Receptor: A Triple Negative Breast Cancer Subtype
Published: June, 2016

Abstract:
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Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth
Published: June, 2016

Abstract: Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct...
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Heat shock represses rRNA synthesis by inactivation of TIF-IA and lncRNA-dependent changes in nucleosome positioning
Published: June, 2016

Abstract: Attenuation of ribosome biogenesis in suboptimal growth environments is crucial for cellular homeostasis and genetic integrity. Here, we show that shutdown of rRNA synthesis in response to elevated temperature is brought about by mechanisms that t...
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Epigenetic inactivation of the CpG demethylase TET1 as a DNA methylation feedback loop in human cancers
Published: May, 2016

Abstract: Promoter CpG methylation is a fundamental regulatory process of gene expression. TET proteins are active CpG demethylases converting 5-methylcytosine to 5-hydroxymethylcytosine, with loss of 5 hmC as an epigenetic hallmark of cancers, indic...
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PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
Published: May, 2016

Abstract: PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeti...
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Functional incompatibility between the generic NF-κB motif and a subtype-specific Sp1III element drives the formation of HIV-1 subtype C viral promoter
Published: May, 2016

Abstract: Of the various genetic subtypes of HIV-1, HIV-2 and SIV, only in subtype C of HIV-1, a genetically variant NF-κB binding site is found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the subtype-ass...
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mTOR transcriptionally and post-transcriptionally regulates Npm1 gene expression to contribute to enhanced proliferation in cells with Pten inactivation
Published: May, 2016

Abstract: The mammalian target of rapamycin (mTOR) plays essential roles in the regulation of growth-related processes such as protein synthesis, cell sizing and metabolism in both normal and pathological growing conditions. These functions of mTOR are thou...
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RESEARCH RESOURCE: Changes in gene expression and Estrogen Receptor cistrome in mouse liver upon acute E2 treatment.
Published: May, 2016

Abstract: Transcriptional regulation by the Estrogen Receptor α (ER) has been investigated mainly in breast cancer cell lines but estrogens such as 17β-Estradiol (E2) exert numerous extra-reproductive effects, particularly in the liver where E2 e...
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MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells
Published: May, 2016

Abstract: Numerous developmentally regulated genes in mouse embryonic stem cells (ESCs) are marked by both active (H3K4me3)- and polycomb group (PcG)-mediated repressive (H3K27me3) histone modifications. This bivalent state is thought to be important for tr...
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PKC-mediated phosphorylation of BCL11B at Serine 2 negatively regulates its interaction with NuRD complexes during CD4+ T cell activation
Published: May, 2016

Abstract: The transcription factor BCL11B/CTIP2 is a major regulatory protein implicated in various aspects of development, function and survival of T cells. MAPK-mediated phosphorylation and SUMOylation modulate BCL11B transcriptional activity, switching i...
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EZH2 is overexpressed in adrenocortical carcinoma and is associated with disease progression.
Published: May, 2016

Abstract: Adrenal Cortex Carcinoma (ACC) is an aggressive tumour with poor prognosis. Common alterations in patients include constitutive WNT/β-catenin signalling and overexpression of the growth factor IGF2. However, the combination of both alteration...
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Kaiso mediates human ICR1 methylation maintenance and H19 transcriptional fine regulation
Published: May, 2016

Abstract: Background Genomic imprinting evolved in a common ancestor to marsupials and eutherian mammals and ensured the transcription of developmentally important genes from defined parental alleles. The regulation of imprinted genes is often mediated b...
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Alteration of Gene Expression, DNA Methylation, and Histone Methylation in Free Radical Scavenging Networks in Adult Mouse Hippocampus following Fetal Alcohol Exposure
Published: May, 2016

Abstract: The molecular basis of Fetal Alcohol Spectrum Disorders (FASD) is poorly understood; however, epigenetic and gene expression changes have been implicated. We have developed a mouse model of FASD characterized by learning and memory impairment and ...
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PAFAH1B1 and the lncRNA NONHSAT073641 maintain an angiogenic phenotype in human endothelial cells
Published: April, 2016

Abstract: AIM: Platelet-activating factor acetyl hydrolase 1B1 (PAFAH1B1, also known as Lis1) is a protein essentially involved in neurogenesis and mostly studied in the nervous system. As we observed a significant expression of PAFAH1B1 in the vascular sy...
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Three Novel Heterozygous Point Mutations of NR3C1 causing Glucocorticoid Resistance
Published: April, 2016

Abstract: Generalized glucocorticoid resistance is associated with glucocorticoid receptor (GR, NR3C1) mutations. Three novel heterozygous missense NR3C1 mutations (R477S, Y478C and L672P) were identified in patients presenting with adrenal incidentalomas, ...
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Chromatin immunoprecipitation from fixed clinical tissues reveals tumor-specific enhancer profiles.
Published: April, 2016

Abstract: Extensive cross-linking introduced during routine tissue fixation of clinical pathology specimens severely hampers chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) analysis from archived tissue samples. This limits t...
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Parental epigenetic asymmetry of PRC2-mediated histone modifications in the Arabidopsis endosperm
Published: April, 2016

Abstract: Parental genomes in the endosperm are marked by differential DNA methylation and are therefore epigenetically distinct. This epigenetic asymmetry is established in the gametes and maintained after fertilization by unknown mechanisms. In this manus...
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EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21
Published: April, 2016

Abstract: The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of th...
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Active and Repressive Chromatin-Associated Proteome after MPA Treatment and the Role of Midkine in Epithelial Monolayer Permeability
Published: April, 2016

Abstract: Mycophenolic acid (MPA) is prescribed to maintain allografts in organ-transplanted patients. However, gastrointestinal (GI) complications, particularly diarrhea, are frequently observed as a side effect following MPA therapy. We recently reported ...
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ACE-score-based Analysis of Temporal miRNA Targetomes During Human Cytomegalovirus Infection Using AGO-CLIP-seq
Published: April, 2016

Abstract: Although temporal regulation of gene expression during the course of infection is known to be critical for determining the outcome of host-virus interactions, systematic temporal analysis of the miRNA targetomes during productive viral infection h...
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Overexpression of caspase 7 is ERα dependent to affect proliferation and cell growth in breast cancer cells by targeting p21(Cip)
Published: April, 2016

Abstract: Caspase 7 (CASP7) expression has important function during cell cycle progression and cell growth in certain cancer cells and is also involved in the development and differentiation of dental tissues. However, the function of CASP7 in breast cance...
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Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time
Published: April, 2016

Abstract: The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the...
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3/16 Epigenetic Programming Alterations in Alligators from Environmentally Contaminated Lakes.
Published: April, 2016

Abstract: Previous studies examining the reproductive health of alligators in Florida lakes indicate that a variety of developmental and health impacts can be attributed to a combination of environmental quality and exposures to environmental contaminants. ...
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BRCA1 positively regulates FOXO3 expression by restricting FOXO3 gene methylation and epigenetic silencing through targeting EZH2 in breast cancer
Published: April, 2016

Abstract: BRCA1 mutation or depletion correlates with basal-like phenotype and poor prognosis in breast cancer but the underlying reason remains elusive. RNA and protein analysis of a panel of breast cancer cell lines revealed that BRCA1 deficiency is assoc...
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The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer
Published: April, 2016

Abstract: Heparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumori...
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Frequency and mitotic heritability of epimutations in Schistosoma mansoni
Published: April, 2016

Abstract: Schistosoma mansoni is a parasitic platyhelminth responsible for intestinal bilharzia. It has a complex life cycle, infecting a freshwater snail of the Biomphalaria genus, and then a mammalian host. Schistosoma mansoni adapts rapidly to new (allop...
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PIAS1 binds p300 and behaves as a coactivator or corepressor of the transcription factor c-Myb dependent on SUMO-status
Published: March, 2016

Abstract: The PIAS proteins (Protein Inhibitor of Activated STATs) constitute a family of multifunctional nuclear proteins operating as SUMO E3 ligases and being involved in a multitude of interactions. They participate in a range of biological processes, a...
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GATA-1 Inhibits PU.1 Gene via DNA and Histone H3K9 Methylation of Its Distal Enhancer in Erythroleukemia
Published: March, 2016

Abstract: GATA-1 and PU.1 are two important hematopoietic transcription factors that mutually inhibit each other in progenitor cells to guide entrance into the erythroid or myeloid lineage, respectively. PU.1 controls its own expression during myelopoiesis ...
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Sequence features accurately predict genome-wide MeCP2 binding in vivo
Published: March, 2016

Abstract: Methyl-CpG binding protein 2 (MeCP2) is critical for proper brain development and expressed at near-histone levels in neurons, but the mechanism of its genomic localization remains poorly understood. Using high-resolution MeCP2-binding data, we sh...
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Zbtb20 promotes astrocytogenesis during neocortical development
Published: March, 2016

Abstract: Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiate...
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Dynamic interplay between locus-specific DNA methylation and hydroxymethylation regulates distinct biological pathways in prostate carcinogenesis
Published: March, 2016

Abstract: Background Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation m...
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Role of Annexin gene and its regulation during zebrafish caudal fin regeneration
Published: March, 2016

Abstract: The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of...
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Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis
Published: March, 2016

Abstract: Radiotherapy is a fundamental part of cancer treatment but its use is limited by the onset of late adverse effects in the normal tissue, especially radiation-induced fibrosis. Since the molecular causes for fibrosis are largely unknown, we analyse...
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Biochemical reconstitution of TET1–TDG–BER-dependent active DNA demethylation reveals a highly coordinated mechanism
Published: March, 2016

Abstract: Cytosine methylation in CpG dinucleotides is an epigenetic DNA modification dynamically established and maintained by DNA methyltransferases and demethylases. Molecular mechanisms of active DNA demethylation began to surface only recently with the...
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Hydroxymethylation of microRNA-365-3p Regulates Nociceptive Behaviors via Kcnh2
Published: March, 2016

Abstract: DNA 5-hydroxylmethylcytosine (5hmC) catalyzed by ten-eleven translocation methylcytosine dioxygenase (TET) occurs abundantly in neurons of mammals. However, the in vivo causal link between TET dysregulation and nociceptive modulation has not been ...
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ArrayNinja: An Open Source Platform for Unified Planning and Analysis of Microarray Experiments
Published: March, 2016

Abstract: Microarray-based proteomic platforms have emerged as valuable tools for studying various aspects of protein function, particularly in the field of chromatin biochemistry. Microarray technology itself is largely unrestricted in regard to printable ...
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Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism
Published: March, 2016

Abstract: Cytosine methylation in CpG dinucleotides is an epigenetic DNA modification dynamically established and maintained by DNA methyltransferases and demethylases. Molecular mechanisms of active DNA demethylation began to surface only recently with the...
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KMT2D regulates specific programs in heart development via histone H3 lysine 4 di-methylation
Published: March, 2016

Abstract: KMT2D, which encodes a histone H3K4 methyltransferase, has been implicated in human congenital heart disease in the context of Kabuki syndrome. However, its role in heart development is not understood. Here, we demonstrate a requirement for KMT2D ...
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BPA-Induced Deregulation Of Epigenetic Patterns: Effects On Female Zebrafish Reproduction
Published: February, 2016

Abstract: Bisphenol A (BPA) is one of the commonest Endocrine Disruptor Compounds worldwide. It interferes with vertebrate reproduction, possibly by inducing deregulation of epigenetic mechanisms. To determine its effects on female reproductive physiology a...
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Genome-wide DNA methylation profile of developing deciduous tooth germ in miniature pigs
Published: February, 2016

Abstract: BACKGROUND: DNA methylation is an important epigenetic modification critical to the regulation of gene expression during development. To date, little is known about the role of DNA methylation in tooth development in large animal models. Thus, ...
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Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses.
Published: February, 2016

Abstract: Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive ...
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GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification
Published: February, 2016

Abstract: Epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, has been implicated to contribute to the molecular heterogeneity of epithelial ovarian cancer (EOC). Here we re...
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Oestrogen receptor β regulates epigenetic patterns at specific genomic loci through interaction with thymine DNA glycosylase.
Published: February, 2016

Abstract: BACKGROUND: DNA methylation is one way to encode epigenetic information and plays a crucial role in regulating gene expression during embryonic development. DNA methylation marks are established by the DNA methyltransferases and, recently, a me...
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Chemical Biology Approaches for Characterization of Epigenetic Regulators
Published: February, 2016

Abstract: Chemical biology approaches are a powerful means to functionally characterize epigenetic regulators such as histone modifying enzymes. We outline experimental protocols and best practices for the cellular characterization and use of “chemica...
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Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.
Published: February, 2016

Abstract: Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic de...
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The JMJD3 Histone Demethylase and the EZH2 Histone Methyltransferase in Prostate Cancer
Published: February, 2016

Abstract: Prostate cancer is themost common cancer in men. It has been clearly established that genetic and epigenetic alterations of histone 3 lysine 27 trimethylation (H3K27me3) are common events in prostate cancer. This mark is deregulated in prostate ca...
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Differential Expression of Genes and DNA Methylation associated with Prenatal Protein Undernutrition by Albumen Removal in an avian model
Published: February, 2016

Abstract: Previously, long-term effects on body weight and reproductive performance have been demonstrated in the chicken model of prenatal protein undernutrition by albumen removal. Introduction of such persistent alterations in phenotype suggests stable c...
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Expression of the MOZ-TIF2 oncoprotein in mice represses senescence.
Published: February, 2016

Abstract: The MOZ-TIF2 translocation, that fuses MOZ (Monocytic Leukemia Zinc finger protein) histone acetyltransferase (HAT) with the nuclear co-activator TIF2, is associated the development of Acute Myeloid Leukemia. We recently showed that in t...
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Role of Growth Arrest and DNA Damage-Inducible, Beta in Alcohol-Drinking Behaviors
Published: February, 2016

Abstract: BACKGROUND: The contribution of epigenetic factors, such as histone acetylation and DNA methylation, to the regulation of alcohol-drinking behavior has been increasingly recognized over the last several years. GADD45b is a protein demonstrated to...
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Protocol for Methylated DNA Immunoprecipitation (MeDIP) Analysis
Published: February, 2016

Abstract: DNA methylation is a fundamental epigenetic mechanism for silencing gene expression by either modifying chromatin structure to a repressive state or interfering with the transcription factors’ binding. DNA methylation primarily occurs at the...
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TET-catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF-dependent alternative splicing.
Published: February, 2016

Abstract: Intragenic 5-methylcytosine and CTCF mediate opposing effects on pre-mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5-methylcytosine evicts CTCF, leading to exon exclusion. However, the mec...
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The dual specificity phosphatase 2 gene is hypermethylated in human cancer and regulated by epigenetic mechanisms
Published: February, 2016

Abstract: Dual specificity phosphatases are a class of tumor-associated proteins involved in the negative regulation of the MAP kinase pathway. Downregulation of the dual specificity phosphatase 2 (DUSP2) has been reported in cancer. Epigenetic si...
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RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine.
Published: January, 2016

Abstract: Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, ...
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Transcriptome-wide distribution and function of RNA hydroxymethylcytosine
Published: January, 2016

Abstract: Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, ...
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Chromatin Immunoprecipitation Assay for the Identification of Arabidopsis Protein-DNA Interactions In Vivo
Published: January, 2016

Abstract: Intricate gene regulatory networks orchestrate biological processes and developmental transitions in plants. Selective transcriptional activation and silencing of genes mediate the response of plants to environmental signals and developmental cues...
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De novo DNA methylation drives 5hmC accumulation in mouse zygotes
Published: January, 2016

Abstract: Zygotic epigenetic reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs ,,,). Here we demonstrate ...
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The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability
Published: January, 2016

Abstract: The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone de...
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DOT1L Activity Promotes Proliferation and Protects Cortical Neural Stem Cells from Activation of ATF4-DDIT3-Mediated ER Stress In Vitro
Published: January, 2016

Abstract: Growing evidence suggests that the lysine methyltransferase DOT1L/KMT4 has important roles in proliferation, survival, and differentiation of stem cells in development and in disease. We investigated the function of DOT1L in neural stem cells (NSC...
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Functional characterization of the hGRαT556I causing Chrousos syndrome
Published: January, 2016

Abstract: BACKGROUND: Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene. A novel case ...
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MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199
Published: December, 2015

Abstract: Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refract...
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cChIP-seq: a robust small-scale method for investigation of histone modifications
Published: December, 2015

Abstract: Background ChIP-seq is highly utilized for mapping histone modifications that are informative about gene regulation and genome annotations. For example, applying ChIP-seq to histone modifications such as H3K4me1 has facilitated generating epige...
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Embryonic transcription is controlled by maternally defined chromatin state
Published: December, 2015

Abstract: Histone-modifying enzymes are required for cell identity and lineage commitment, however little is known about the regulatory origins of the epigenome during embryonic development. Here we generate a comprehensive set of epigenome reference maps, ...
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Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal.
Published: December, 2015

Abstract: Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencin...
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Germline organization in Strongyloides nematodes reveals alternative differentiation and regulation mechanisms.
Published: December, 2015

Abstract: Nematodes of the genus Strongyloides are important parasites of vertebrates including man. Currently, little is known about their germline organization or reproductive biology and how this influences their parasitic life strategies. Here, we analy...
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Independent Mechanisms Target SMCHD1 to Trimethylated Histone H3 Lysine 9-Modified Chromatin and the Inactive X Chromosome
Published: December, 2015

Abstract: The chromosomal protein SMCHD1 plays an important role in epigenetic silencing at diverse loci, including the inactive X chromosome, imprinted genes, and the facioscapulohumeral muscular dystrophy locus. Although homology with canonical SMC family...
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DNA methylation profiling: comparison of genome-wide sequencing methods and the Infinium Human Methylation 450 Bead Chip
Published: December, 2015

Abstract: AIMS: To compare the performance of four sequence-based and one microarray methods for DNA methylation profiling. METHODS: DNA from two cell lines were profiled by reduced representation bisulfite sequencing, methyl capture sequencing (SS-Met...
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A highly conserved NF-κB-responsive enhancer is critical for thymic expression of Aire in mice
Published: December, 2015

Abstract: Autoimmune regulator (Aire) has a unique expression pattern in thymic medullary epithelial cells (mTECs), in which it plays a critical role in the activation of tissue-specific antigens. The expression of Aire in mTECs is activated by receptor act...
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Oxidative DNA damage in mouse sperm chromosomes: Size matters.
Published: December, 2015

Abstract: Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models ...
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Transient generalized glucocorticoid hypersensitivity
Published: December, 2015

Abstract: BACKGROUND: Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itsel...
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The Cytoplasmic Region of Plasmodium falciparum SURFIN4.2 Is Required for Transport from Maurer’s Clefts to the Red Blood Cell Surface
Published: December, 2015

Abstract: Background: Plasmodium, the causative agent of malaria, exports many proteins to the surface of the infected red blood cell (iRBC) in order to modify it toward a structure more suitable for parasite development and survival. One such exported pr...
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Dynamic changes in histone modifications precede de novo DNA methylation in oocytes
Published: December, 2015

Abstract: Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a nu...
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Brg1 coordinates multiple processes during retinogenesis and is a tumor suppressor in retinoblastoma
Published: December, 2015

Abstract: Retinal development requires precise temporal and spatial coordination of cell cycle exit, cell fate specification, cell migration and differentiation. When this process is disrupted, retinoblastoma, a developmental tumor of the retina, can form. ...
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Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization
Published: December, 2015

Abstract: BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from re...
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Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells
Published: November, 2015

Abstract: Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels an...
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Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance
Published: November, 2015

Abstract: Mammalian SWI/SNF [also called Brg/Brahma-associated factors (BAFs)] are evolutionarily conserved chromatin-remodeling complexes regulating gene transcription programs during development and stem cell differentiation. BAF complexes contain an ATP ...
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Occupancy of RNA Polymerase II Phosphorylated on Serine 5 (RNAP S5P) and RNAP S2P on Varicella-Zoster Virus Genes 9, 51, and 66 Is Independent of Transcript Abundance and Polymerase Location within the Gene
Published: November, 2015

Abstract: Regulation of gene transcription in varicella-zoster virus (VZV), a ubiquitous human neurotropic alphaherpesvirus, requires coordinated binding of multiple host and virus proteins onto specific regions of the virus genome. Chromatin immunoprecipit...
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Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation
Published: November, 2015

Abstract: Histone H3K36 trimethylation (H3K36me3) is frequently lost in multiple cancer types, identifying it as an important therapeutic target. Here we identify a synthetic lethal interaction in which H3K36me3-deficient cancers are acutely sensitive to WE...
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CRISPR-Mediated Gene Targeting of Human Induced Pluripotent Stem Cells
Published: November, 2015

Abstract: CRISPR/Cas9 nuclease systems can create double-stranded DNA breaks at specific sequences to efficiently and precisely disrupt, excise, mutate, insert, or replace genes. However, human embryonic stem cells and induced pluripotent stem cells (iPSCs)...
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Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells
Published: November, 2015

Abstract: Molecular mechanisms underlying terminal differentiation of B cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets a...
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The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth
Published: November, 2015

Abstract: Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epiderma...
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Spatial Interplay between Polycomb and Trithorax Complexes Controls Transcriptional Activity in T Lymphocytes
Published: November, 2015

Abstract: Trithorax group (TrxG) and Polycomb group (PcG) proteins are two mutually antagonistic chromatin modifying complexes, however, how they together mediate transcriptional counter-regulation remains unknown. Genome-wide analysis revealed that binding...
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Sox4 Expression Confers Bladder Cancer Stem Cell Properties and Predicts for Poor Patient Outcome
Published: November, 2015

Abstract: Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). We have previously found that amplification of chromosome 6p22 is sig...
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A gene expression signature identifying transient DNMT1 depletion as a causal factor of cancer-germline gene activation in melanoma
Published: October, 2015

Abstract: Many human tumors show aberrant activation of a group of germline-specific genes, termed cancer-germline (CG) genes, several of which appear to exert oncogenic functions. Although activation of CG genes in tumors has been linked to promoter DNA de...
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Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression
Published: October, 2015

Abstract: α-synuclein, a protein enriched in Lewy bodies and highly implicated in neurotoxicity in Parkinson's disease, is distributed both at nerve terminals and in the cell nucleus. Here we show that a nuclear derivative of α-synuclein induces...
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Optimized method for methylated DNA immuno-precipitation
Published: October, 2015

Abstract: Methylated DNA immunoprecipitation (MeDIP) is one of the most widely used methods to evaluate DNA methylation on a whole genome scale, and involves the capture of the methylated fraction of the DNA by an antibody specific to methyl-cytosine. MeDIP...
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Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes
Published: October, 2015

Abstract: Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed...
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A geminivirus-based guide RNA delivery system for CRISPR/Cas9 mediated plant genome editing
Published: October, 2015

Abstract: CRISPR/Cas has emerged as potent genome editing technology and has successfully been applied in many organisms, including several plant species. However, delivery of genome editing reagents remains a challenge in plants. Here, we report a virus-ba...
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The genetic association of RUNX3 with ankylosing spondylitis can be explained by allele-specific effects on IRF4 recruitment that alter gene expression
Published: October, 2015

Abstract: The authors sought to identify the functional basis for the genetic association of single nucleotide polymorphisms (SNP), upstream of the RUNX3 promoter, with ankylosing spondylitis (AS). They performed conditional analysis of genetic association ...
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VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach
Published: October, 2015

Abstract: AIMS: To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer. MATERIALS & METHODS: Non-small-cell lung cancer cells were screened for the VEGF rece...
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ClpX stimulates the mitochondrial unfolded protein response (UPRmt) in mammalian cells
Published: October, 2015

Abstract: Proteostasis is crucial for life and maintained by cellular chaperones and proteases. One major mitochondrial protease is the ClpXP complex, which is comprised of a catalytic ClpX subunit and a proteolytic ClpP subunit. Based on two separate obser...
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Arabidopsis CMT3 activity is positively regulated by AtSIZ1-mediated sumoylation
Published: October, 2015

Abstract: The activities of mammalian DNA and histone methyltransferases are regulated by post-translational modifications such as phosphorylation and sumoylation; however, it is unclear how the activities of these enzymes are regulated at the post-translat...
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Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis
Published: October, 2015

Abstract: Mutations in the gene encoding the KMT2D (or MLL2) methyltransferase are highly recurrent and occur early during tumorigenesis in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the functional consequences of these mut...
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Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome
Published: October, 2015

Abstract: The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genom...
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Endothelial Msx1 transduces hemodynamic changes into an arteriogenic remodeling response.
Published: September, 2015

Abstract: Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction re...
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Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape
Published: September, 2015

Abstract: BACKGROUND: Previously, a role was demonstrated for transcription in the acquisition of DNA methylation at imprinted control regions in oocytes. Definition of the oocyte DNA methylome by whole genome approaches revealed that the majority of met...
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A high-resolution imaging approach to investigate chromatin architecture in complex tissues
Published: September, 2015

Abstract: We present ChromATin, a quantitative high-resolution imaging approach for investigating chromatin organization in complex tissues. This method combines analysis of epigenetic modifications by immunostaining, localization of specific DNA sequen...
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Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure
Published: September, 2015

Abstract: RATIONALE: In chronic heart failure, increased adrenergic activation contributes to structural remodeling and altered gene expression. Although adrenergic signaling alters histone modifications, it is unknown, whether it also affects other epigen...
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Immunohistochemical Detection of Oxidized Forms of 5-Methylcytosine in Embryonic and Adult Brain Tissue
Published: September, 2015

Abstract: DNA methylation (5-methylcytosine, 5mC) is a major epigenetic modification of the eukaryotic genome associated with gene repression. Ten-eleven translocation proteins (Tet1/2/3) can oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (...
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Genome-wide p63-regulated gene expression in differentiating epidermal keratinocytes
Published: September, 2015

Abstract: The transcription factor p63 is a key regulator in epidermal keratinocyte proliferation and differentiation. However, the role of p63 in gene regulation during these processes is not well understood. To investigate this, we recently generated geno...
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Chromatin assembly factor CAF-1 represses priming of plant defence response genes
Published: September, 2015

Abstract: Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter...
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The Epigenome of Schistosoma mansoni Provides Insight about How Cercariae Poise Transcription until Infection
Published: August, 2015

Abstract: BACKGROUND: Chromatin structure can control gene expression and can define specific transcription states. For example, bivalent methylation of histone H3K4 and H3K27 is linked to poised transcription in vertebrate embryonic stem cells (ESC). It...
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Spatiotemporal control of estrogen-responsive transcription in ERα-positive breast cancer cells.
Published: August, 2015

Abstract: Recruitment of transcription machinery to target promoters for aberrant gene expression has been well studied, but underlying control directed by distant-acting enhancers remains unclear in cancer development. Our previous study demonstrated that ...
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Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection.
Published: August, 2015

Abstract: CRISPR-Cas9 systems provide a platform for high efficiency genome editing that are enabling innovative applications of mammalian cell engineering. However, the delivery of Cas9 and synthesis of guide RNA (gRNA) remain as steps that can limit overa...
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Polycomb RING1A- and RING1B-dependent histone H2A monoubiquitylation at pericentromeric regions promotes S-phase progression
Published: August, 2015

Abstract: The functions of polycomb products extend beyond their well-known activity as transcriptional regulators to include genome duplication processes. Polycomb activities during DNA replication and DNA damage repair are unclear, particularly without in...
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C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis
Published: August, 2015

Abstract: Highlights C/EBPα activates two classes of prospective myeloid enhancers in B cells Pre-existing enhancers are bound by PU.1 and become hyper-activated by C/EBPα C/EBPα acts as a pioneer factor with delayed kinetics on...
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Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress
Published: August, 2015

Abstract: The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here...
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Condensin targets and reduces unwound DNA structures associated with transcription in mitotic chromosome condensation
Published: July, 2015

Abstract: Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells. Here we show that condensin, which is essential for assembling condensed chromosomes, helps to pre...
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Non-coding recurrent mutations in chronic lymphocytic leukaemia.
Published: July, 2015

Abstract: Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases ...
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Deciphering the principles that govern mutually exclusive expression of Plasmodium falciparum clag3 genes
Published: July, 2015

Abstract: The product of the Plasmodium falciparum genes clag3.1 and clag3.2 plays a fundamental role in malaria parasite biology by determining solute transport into infected erythrocytes. Expression of the two clag3 genes is mutually exclusive, such that ...
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The complex pattern of epigenomic variation between natural yeast strains at single-nucleosome resolution.
Published: July, 2015

Abstract: BACKGROUND: Epigenomic studies on humans and model species have revealed substantial inter-individual variation in histone modification profiles. However, the pattern of this variation has not been precisely characterized, particularly regardin...
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The oncofusion protein FUS-ERG targets key hematopoietic regulators and modulates the all-trans retinoic acid signaling pathway in t(16;21) acute myeloid leukemia.
Published: July, 2015

Abstract: The ETS transcription factor ERG has been implicated as a major regulator of both normal and aberrant hematopoiesis. In acute myeloid leukemias harboring t(16;21), ERG function is deregulated due to a fusion with FUS/TLS resulting in the expressio...
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DNA methylation directs functional maturation of pancreatic β cells
Published: July, 2015

Abstract: Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capa...
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Transcription factor p63 bookmarks and regulates dynamic enhancers during epidermal differentiation
Published: July, 2015

Abstract: The transcription factor p63 plays a pivotal role in keratinocyte proliferation and differentiation in the epidermis. However, how p63 regulates epidermal genes during differentiation is not yet clear. Using epigenome profiling of differentiating ...
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Gadd45b and N-methyl-D-aspartate induced DNA demethylation in postmitotic neurons.
Published: June, 2015

Abstract: AIM: In nondividing neurons examine the role of Gadd45b in active 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) removal at a gene promoter highly implicated in mental illnesses and cognition, Bdnf. MATERIALS & METHODS: Mouse prima...
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Active human nucleolar organizer regions are interspersed with inactive rDNA repeats in normal and tumor cells.
Published: June, 2015

Abstract: AIM: The synthesis of rRNA is a key determinant of normal and malignant cell growth and subject to epigenetic regulation. Yet, the epigenomic features of rDNA arrays clustered in nucleolar organizer regions are largely unknown. We set out to ex...
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Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses.
Published: June, 2015

Abstract: Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but...
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Gene chip analysis of Arabidopsis thaliana genomic DNA methylation and gene expression in response to carbendazim.
Published: June, 2015

Abstract: OBJECTIVES: To examine the effects of carbendazim on Arabidopsis genomic DNA methylation and gene expression. RESULTS: Carbendazim caused widespread changes in gene loci methylation and gene expression. With 0.1 mM (D2) and 0.2 mM (D3) carbendazim...
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A localized nucleolar DNA damage response facilitates recruitment of the homology-directed repair machinery independent of cell cycle stage.
Published: June, 2015

Abstract: DNA double-strand breaks (DSBs) are repaired by two main pathways: nonhomologous end-joining and homologous recombination (HR). Repair pathway choice is thought to be determined by cell cycle timing and chromatin context. Nucleoli, prominent nucle...
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Allele-specific binding of ZFP57 in the epigenetic regulation of imprinted and non-imprinted monoallelic expression
Published: May, 2015

Abstract: BACKGROUND: Selective maintenance of genomic epigenetic imprints during pre-implantation development is required for parental origin-specific expression of imprinted genes. The Kruppel-like zinc finger protein ZFP57 acts as a factor necessary f...
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Composite macroH2A/NRF-1 Nucleosomes Suppress Noise and Generate Robustness in Gene Expression.
Published: May, 2015

Abstract: The histone variant macroH2A (mH2A) has been implicated in transcriptional repression, but the molecular mechanisms that contribute to global mH2A-dependent genome regulation remain elusive. Using chromatin immunoprecipitation sequencing (ChIP-seq...
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Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency.
Published: May, 2015

Abstract: Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs ...
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Erosion of X Chromosome Inactivation in Human Pluripotent Cells Initiates with XACT Coating and Depends on a Specific Heterochromatin Landscape.
Published: May, 2015

Abstract: Human pluripotent stem cells (hPSCs) display extensive epigenetic instability, particularly on the X chromosome. In this study, we show that, in hPSCs, the inactive X chromosome has a specific heterochromatin landscape that predisposes it to erosi...
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Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential.
Published: May, 2015

Abstract: The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemia has a consistently poor outcome. One of the most common translocation partners is AF9 (MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79...
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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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Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells.
Published: May, 2015

Abstract: DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Here we inactivated all three catalytically active DNA methyltransferases (DNMTs) in human embryonic stem cells (ESCs) using...
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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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Identification of Critical Elements for Regulation of Inorganic Pyrophosphatase (PPA1) in MCF7 Breast Cancer Cells.
Published: April, 2015

Abstract: Cytosolic inorganic pyrophosphatase plays an important role in the cellular metabolism by hydrolyzing inorganic pyrophosphate (PPi) formed as a by-product of various metabolic reactions. Inorganic pyrophosphatases are known to be associated with i...
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Opposite expression of CYP51A1 and its natural antisense transcript AluCYP51A1 in adenovirus type 37 infected retinal pigmented epithelial cells.
Published: April, 2015

Abstract: Cytochrome P450 family member CYP51A1 is a key enzyme in cholesterol biosynthesis whose deregulation is implicated in numerous diseases, including retinal degeneration. Here we describe that HAdV-37 infection leads to downregulation of CYP51A1 exp...
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Deciphering the role of Polycomb Repressive Complex 1 (PRC1) variants in regulating the acquisition of flowering competence in Arabidopsis.
Published: April, 2015

Abstract: Polycomb Group (PcG) proteins play important roles in regulating developmental phase transitions in plants; however, little is known about the role the PcG machinery in regulating the transition from juvenile to adult phase. Here, we show that Ara...
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Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis
Published: April, 2015

Abstract: DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute mye...
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A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage.
Published: April, 2015

Abstract: Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One ...
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Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch.
Published: April, 2015

Abstract: Human cytomegalovirus (HCMV) is a highly prevalent pathogen that induces life-long infections notably through the establishment of latency in hematopoietic stem cells (HSC). Bouts of reactivation are normally controlled by the immune system, but c...
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NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1.
Published: April, 2015

Abstract: The circadian clock controls the transcription of hundreds of genes through specific chromatin-remodeling events. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) coordinates recruitment of CLOCK-BMAL1 activator complexes to chromatin...
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Characterization of the nasopharyngeal carcinoma methylome identifies aberrant disruption of key signaling pathways and methylated tumor suppressor genes.
Published: April, 2015

Abstract: Aims: Nasopharyngeal carcinoma (NPC) is a common tumor consistently associated with Epstein-Barr virus infection and prevalent in South China, including Hong Kong, and southeast Asia. Current genomic sequencing studies found only rare mutations in...
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Genome-wide CIITA-binding profile identifies sequence preferences that dictate function versus recruitment
Published: March, 2015

Abstract: The class II transactivator (CIITA) is essential for the expression of major histocompatibility complex class II (MHC-II) genes; however, the role of CIITA in gene regulation outside of MHC-II biology is not fully understood. To comprehensively ma...
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Genome-wide CIITA-binding profile identifies sequence preferences that dictate function versus recruitment.
Published: March, 2015

Abstract: The class II transactivator (CIITA) is essential for the expression of major histocompatibility complex class II (MHC-II) genes; however, the role of CIITA in gene regulation outside of MHC-II biology is not fully understood. To comprehensively ma...
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Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
Published: March, 2015

Abstract: CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, th...
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Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis.
Published: March, 2015

Abstract: Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer c...
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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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Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells.
Published: March, 2015

Abstract: To combat hostile viruses, bacteria and archaea have evolved a unique antiviral defense system composed of clustered regularly interspaced short palindromic repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9 system dev...
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Genome-wide mapping reveals conservation of promoter DNA methylation following chicken domestication.
Published: March, 2015

Abstract: It is well-known that environment influences DNA methylation, however, the extent of heritable DNA methylation variation following animal domestication remains largely unknown. Using meDIP-chip we mapped the promoter methylomes for 23,316 genes in...
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An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo.
Published: March, 2015

Abstract: The CRISPR/Cas9 technology enables the introduction of genomic alterations into almost any organism; however, systems for efficient and inducible gene modification have been lacking, especially for deletion of essential genes. Here, we describe a ...
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An inducible lentiviral guide RNA platform enables the identification of tumor-essential genes and tumor-promoting mutations in vivo
Published: March, 2015

Abstract: The CRISPR/Cas9 technology enables the introduction of genomic alterations into almost any organism; however, systems for efficient and inducible gene modification have been lacking, especially for deletion of essential genes. Here, we describe a ...
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Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.
Published: February, 2015

Abstract: Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarco...
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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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A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity.
Published: February, 2015

Abstract: The p53 family and its cofactors are potent inducers of apoptosis and form a barrier to cancer. Here, we investigated the impact of the supposedly inhibitory member of the apoptosis-stimulating protein of p53, iASPP, on the activity of the p53 hom...
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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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Genome-wide and single-cell analyses reveal a context dependent relationship between CBP recruitment and gene expression.
Published: February, 2015

Abstract: Genome-wide distribution of histone H3K18 and H3K27 acetyltransferases, CBP (CREBBP) and p300 (EP300), is used to map enhancers and promoters, but whether these elements functionally require CBP/p300 remains largely uncertain. Here we compared glo...
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Stable X Chromosome Reactivation in Female Human Induced Pluripotent Stem Cells.
Published: January, 2015

Abstract: In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female h...
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Embryonic stem cell differentiation requires full length Chd1.
Published: January, 2015

Abstract: The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the ef...
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Genome-wide DNA methylation analysis in Graves' disease.
Published: January, 2015

Abstract: As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathoge...
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An ultra-low-input native ChIP-seq protocol for genome-wide profiling of rare cell populations.
Published: January, 2015

Abstract: Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required t...
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Ultra-low-input native ChIP-seq for rare cell populations
Published: January, 2015

Abstract: Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required t...
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A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus.
Published: January, 2015

Abstract: Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. ...
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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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The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer.
Published: January, 2015

Abstract: Endocrine therapy has successfully been used to treat estrogen receptor (ER)-positive breast cancer, but this invariably fails with cancers becoming refractory to treatment. Emerging evidence has suggested that fluctuations in ER co-regulatory pro...
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TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells.
Published: January, 2015

Abstract: TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruse...
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iRNA-seq: computational method for genome-wide assessment of acute transcriptional regulation from total RNA-seq data.
Published: January, 2015

Abstract: RNA-seq is a sensitive and accurate technique to compare steady-state levels of RNA between different cellular states. However, as it does not provide an account of transcriptional activity per se, other technologies are needed to more precisely d...
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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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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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Differential distribution of HP1 proteins after trichostatin a treatment influences chromosomal stability in HCT116 and WI-38 cells
Published: December, 2014

Abstract: Abstract Background Heterochromatin protein 1 (HP1) is important in the establishment, propagation, and maintenance of constitutive heterochromatin, especi ally at the pericentromeric region. HP1 might participate in recruiting and directing Mis12...
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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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Identification of SCAN Domain Zinc-Finger Gene ZNF449 as a Novel Factor of Chondrogenesis.
Published: December, 2014

Abstract: Transcription factors SOX9, SOX5 and SOX6 are indispensable for generation and differentiation of chondrocytes. However, molecular mechanisms to induce the SOX genes are poorly understood. To address this issue, we previously determined the human ...
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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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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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An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins.
Published: December, 2014

Abstract: DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 ...
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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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lncRNA Maturation to Initiate Heterochromatin Formation in the Nucleolus Is Required for Exit from Pluripotency in ESCs.
Published: December, 2014

Abstract: The open chromatin of embryonic stem cells (ESCs) condenses into repressive heterochromatin as cells exit the pluripotent state. How the 3D genome organization is orchestrated and implicated in pluripotency and lineage specification is not underst...
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Endonuclease G preferentially cleaves 5-hydroxymethylcytosine-modified DNA creating a substrate for recombination.
Published: December, 2014

Abstract: 5-hydroxymethylcytosine (5hmC) has been suggested to be involved in various nucleic acid transactions and cellular processes, including transcriptional regulation, demethylation of 5-methylcytosine and stem cell pluripotency. We have identified an...
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Hypermethylation of cox5a promoter is associated with mitochondrial dysfunction in skeletal muscle of high fat diet-induced insulin resistant rats.
Published: December, 2014

Abstract: High-fat diet (HFD) is an environmental factor that contributes to the pathogenesis of obesity and type 2 diabetes. A number of genes influencing oxidative phosphorylation (OXPHOS) were found to be downregulated in skeletal muscle of humans and ra...
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Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation.
Published: December, 2014

Abstract: Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their bin...
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Acute Depletion Redefines the Division of Labor among DNA Methyltransferases in Methylating the Human Genome.
Published: November, 2014

Abstract: Global patterns of DNA methylation, mediated by the DNA methyltransferases (DNMTs), are disrupted in all cancers by mechanisms that remain largely unknown, hampering their development as therapeutic targets. Combinatorial acute depletion of all DN...
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Genome-wide identification of aberrantly methylated promoters in ovarian tissue of prenatally androgenized rats.
Published: November, 2014

Abstract: OBJECTIVE: To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS). DESIGN: Animal model. SETTING: University-affiliated laboratory. ANIMAL(S): Sprague-Dawley rats. INTERVENTION(S)...
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A B-cell targeting virus disrupts potentially protective genomic methylation patterns in lymphoid tissue by increasing global 5-hydroxmethylcytosine levels
Published: October, 2014

Abstract: The mechanisms by which viruses modulate the immune system include changes in host genomic methylation. 5-hydroxmethylcytosine (5hmC) is the catalytic product of the Tet (Ten-11 translocation) family of enzymes and may serve as an intermediate of ...
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The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer.
Published: October, 2014

Abstract: The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen rec...
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Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs.
Published: October, 2014

Abstract: Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct ...
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White matter tract and glial-associated changes in 5-hydroxymethylcytosine following chronic cerebral hypoperfusion.
Published: October, 2014

Abstract: White matter abnormalities due to age-related cerebrovascular alterations is a common pathological hallmark associated with functional impairment in the elderly which has been modeled in chronically hypoperfused mice. 5-Methylcytosine (5mC) and it...
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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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Active and passive demethylation of male and female pronuclear DNA in the Mammalian zygote.
Published: October, 2014

Abstract: The epigenomes of mammalian sperm and oocytes, characterized by gamete-specific 5-methylcytosine (5mC) patterns, are reprogrammed during early embryogenesis to establish full developmental potential. Previous studies have suggested that the patern...
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Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer.
Published: October, 2014

Abstract: The anti-tuberculosis-vaccine Bacillus Calmette-Guérin (BCG) is the most widely used vaccine in the world. In addition to its effects against tuberculosis, BCG vaccination also induces non-specific beneficial effects against certain forms of malig...
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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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The specific alteration of histone methylation profiles by DZNep during early zebrafish development.
Published: September, 2014

Abstract: Early embryo development constitutes a unique opportunity to study acquisition of epigenetic marks, including histone methylation. This study investigates the in vivo function and specificity of 3-deazaneplanocin A (DZNep), a promising anti-cancer...
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SET8 methyltransferase activity during the DNA double-strand break response is required for recruitment of 53BP1
Published: September, 2014

Abstract: DNA double-strand breaks (DSBs) activate a signaling pathway known as the DNA damage response (DDR) which via protein–protein interactions and post-translational modifications recruit signaling proteins, such as 53BP1, to chromatin flanking the le...
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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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Spontaneous sleep-wake cycle and sleep deprivation differently induce Bdnf1, Bdnf4 and Bdnf9a DNA methylation and transcripts levels in the basal forebrain and frontal cortex in rats.
Published: September, 2014

Abstract: Brain-derived neurotrophic factor (Bdnf) regulates neuronal plasticity, slow wave activity and sleep homeostasis. Environmental stimuli control Bdnf expression through epigenetic mechanisms, but there are no data on epigenetic regulation of Bdnf b...
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Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes.
Published: September, 2014

Abstract: BackgroundIdentification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized a...
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Pcgf6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ES cells and functions in IPS reprogramming.
Published: September, 2014

Abstract: Polycomb group (PcG) proteins comprise evolutionary conserved factors with essential functions for embryonic development and adult stem cells. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate...
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Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.
Published: September, 2014

Abstract: Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin la...
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The cytokine TGF-β co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells.
Published: September, 2014

Abstract: Understanding the developmental mechanisms of follicular helper T cells (TFH cells) in humans is relevant to the clinic. However, the factors that drive the differentiation of human CD4(+) helper T cells into TFH cells remain largely undefined. He...
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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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Long Noncoding RNA TARID Directs Demethylation and Activation of the Tumor Suppressor TCF21 via GADD45A.
Published: August, 2014

Abstract: DNA methylation is a dynamic and reversible process that governs gene expression during development and disease. Several examples of active DNA demethylation have been documented, involving genome-wide and gene-specific DNA demethylation. How deme...
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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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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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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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The histone variant composition of centromeres is controlled by the pericentric heterochromatin state during the cell cycle.
Published: August, 2014

Abstract: Correct chromosome segregation requires a unique chromatin environment at centromeres and in their vicinity. Here, we address how the deposition of canonical H2A and H2A.Z histone variants is controlled at pericentric heterochromatin (PHC). Wherea...
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Epigenetics and the Evolution of Darwin's Finches.
Published: July, 2014

Abstract: The prevailing theory for the molecular basis of evolution involves genetic mutations that ultimately generate the heritable phenotypic variation on which natural selection acts. However, epigenetic transgenerational inheritance of phenotypic vari...
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Changes in histone methylation and acetylation during microspore reprogramming to embryogenesis occur concomitantly with Bn HKMT and Bn HAT expression and are associated with cell totipotency, proliferation, and differentiation in Brassica napus.
Published: July, 2014

Abstract: In response to stress treatments, microspores can be reprogrammed to become totipotent cells that follow an embryogenic pathway producing haploid and double-haploid embryos which are important biotechnological tools in plant breeding. Recent studi...
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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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Development of a lentivirus vector-based assay for non-destructive monitoring of cell fusion activity.
Published: July, 2014

Abstract: Cell-to-cell fusion can be quantified by endowing acceptor and donor cells with latent reporter genes/proteins and activators of these genes/proteins, respectively. One way to accomplish this goal is by using a bipartite lentivirus vector (LV)-bas...
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PHD and TFIIS-Like Domains of the Bye1 Transcription Factor Determine Its Multivalent Genomic Distribution.
Published: July, 2014

Abstract: The BYpass of Ess1 (Bye1) protein is a putative S. cerevisiae transcription factor homologous to the human cancer-associated PHF3/DIDO family of proteins. Bye1 contains a Plant Homeodomain (PHD) and a TFIIS-like domain. The Bye1 PHD finger interac...
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Prenatal Exposure to BPA Alters the Epigenome of the Rat Mammary Gland and Increases the Propensity to Neoplastic Development.
Published: July, 2014

Abstract: Exposure to environmental estrogens (xenoestrogens) may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA) leaches from plastic food/b...
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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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GENOME-WIDE SCREEN OF PROMOTER METHYLATION IDENTIFIES NOVEL MARKERS IN DIET-INDUCED OBESE MICE.
Published: July, 2014

Abstract: OBJECTIVE: To investigate the genome-wide promoter methylation and gene expression for the identification of methylation markers in obesity. METHODS: Using a high-fat, diet-induced obese mouse model, we performed comprehensive DNA methylation prof...
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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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Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation.
Published: June, 2014

Abstract: DNA methylation is a central epigenetic modification in mammals, with essential roles in development and disease. De novo DNA methyltransferases establish DNA methylation patterns in specific regions within the genome by mechanisms that remain poo...
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Analysis of the leaf methylomes of parents and their hybrids provides new insight into hybrid vigor in Populus deltoides
Published: June, 2014

Abstract: Background Plants with heterosis/hybrid vigor perform better than their parents in many traits. However, the biological mechanisms underlying heterosis remain unclear. To investigate the significance of DNA methylation to heterosis, a comprehensi...
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Exposure to Hycanthone alters chromatin structure around specific gene functions and specific repeats in Schistosoma mansoni
Published: June, 2014

Abstract: Schistosoma mansoni is a parasitic plathyhelminth responsible for intestinal schistosomiasis (or bilharziasis), a disease affecting 67 million people worldwide and causing an important economic burden. The schistosomicides hycanthone, and its late...
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Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment.
Published: June, 2014

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

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

Abstract: Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the suc...
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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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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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Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines.
Published: June, 2014

Abstract: BACKGROUND: Originating from Primordial Germ Cells/gonocytes and developing via a precursor lesion called Carcinoma In Situ (CIS), Germ Cell Cancers (GCC) are the most common cancer in young men, subdivided in seminoma (SE) and non-seminoma (NS). ...
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Ezh2 regulates transcriptional and posttranslational expression of T-bet and promotes Th1 cell responses mediating aplastic anemia in mice.
Published: June, 2014

Abstract: Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-γ-producing Th1 CD4(+) T cells mediate the immune destruction of hematopoietic cells, and they are central to the pathogenesis. However, the molecular even...
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DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells.
Published: June, 2014

Abstract: The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. H...
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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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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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The LIM domain protein nTRIP6 recruits the mediator complex to AP-1-regulated promoters.
Published: May, 2014

Abstract: Several LIM domain proteins regulate transcription. They are thought to act through their LIM protein-protein interaction domains as adaptors for the recruitment of transcriptional co-regulators. An intriguing example is nTRIP6, the nuclear isofor...
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Sleep Fragmentation During Late Gestation Induces Metabolic Perturbations and Epigenetic Changes in Adiponectin Gene Expression in Male Adult Offspring Mice.
Published: May, 2014

Abstract: Sleep fragmentation (SF) is a common condition among pregnant women, particularly during late gestation. Gestational perturbations promote the emergence of adiposity and metabolic disease risk in offspring, most likely via epigenetic modifications...
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Nitric oxide-induced neuronal to glial lineage fate-change depends on NRSF/REST function in neural progenitor cells.
Published: May, 2014

Abstract: Degeneration of CNS tissue commonly occurs during neuroinflammatory conditions, such as multiple sclerosis (MS) and neurotrauma. During such conditions, neural stem/progenitor cell (NPC) populations have been suggested to provide new cells to dege...
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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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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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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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Estrogen receptor ligands ameliorate fatty liver through a nonclassical estrogen receptor/Liver X receptor pathway in mice.
Published: May, 2014

Abstract: UNLABELLED: Liver X receptor (LXR) activation stimulates triglyceride (TG) accumulation in the liver. Several lines of evidence indicate that estradiol-17β (E2) reduces TG levels in the liver; however, the molecular mechanism underlying the E2 eff...
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Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis.
Published: May, 2014

Abstract: The Developmental Origins of Health and Disease hypothesis holds that alterations to homeostasis during critical periods of development can predispose individuals to adult-onset chronic diseases such as diabetes and metabolic syndrome. It remains ...
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IL-13Rα2 mediates PNR-induced migration and metastasis in ERα-negative breast cancer.
Published: April, 2014

Abstract: Emerging evidence has linked photoreceptor cell-specific nuclear receptor (PNR/NR2E3), an orphan nuclear hormone receptor, to human breast cancer. PNR was shown to be a transcriptional activator of estrogen receptor-α (ERα) in ERα-positive breast ...
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Context-Selective Death of Acute Myeloid Leukemia Cells Triggered by the Novel Hybrid Retinoid-HDAC Inhibitor MC2392.
Published: April, 2014

Abstract: HDAC inhibitors (HDACi) are widely used in the clinic to sensitize tumorigenic cells for treatment with other anticancer compounds. The major drawback of HDACi is the broad inhibition of the plethora of HDAC-containing complexes. In acute promyelo...
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LSD1 Neurospecific Alternative Splicing Controls Neuronal Excitability in Mouse Models of Epilepsy.
Published: April, 2014

Abstract: Alternative splicing in the brain is dynamic and instrumental to adaptive changes in response to stimuli. Lysine-specific demethylase 1 (LSD1/KDM1A) is a ubiquitously expressed histone H3Lys4 demethylase that acts as a transcriptional co-repressor...
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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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TAL effector-mediated genome visualization (TGV).
Published: April, 2014

Abstract: The three-dimensional remodeling of chromatin within nucleus is being recognized as determinant for genome regulation. Recent technological advances in live imaging of chromosome loci begun to explore the biological roles of the movement of the ch...
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Differential RISC association of endogenous human microRNAs predicts their inhibitory potential.
Published: April, 2014

Abstract: It has previously been assumed that the generally high stability of microRNAs (miRNAs) reflects their tight association with Argonaute (Ago) proteins, essential components of the RNA-induced silencing complex (RISC). However, recent data have sugg...
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Folic acid stimulation of neural stem cell proliferation is associated with altered methylation profile of PI3K/Akt/CREB.
Published: April, 2014

Abstract: Proliferation of neural stem cells (NSCs) is required for development and repair in the nervous system. NSC amplification in vitro is a necessary step towards using NSC transplantation therapy to treat neurodegenerative diseases. Folic acid (FA) h...
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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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Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.
Published: April, 2014

Abstract: Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNA...
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Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene regulation.
Published: March, 2014

Abstract: STAT (Signal Transducer and Activator of Transcription) transcription factors are constitutively activated in most hematopoietic cancers. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in ...
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Overexpressed homeobox B9 regulates oncogenic activities by transforming growth factor-β1 in gliomas.
Published: March, 2014

Abstract: Glioma is the leading cause of deaths related to tumors in the central nervous system. The mechanisms of gliomagenesis remain elusive to date. Homeobox B9 (HOXB9) has a crucial function in the regulation of gene expression and cell survival, but i...
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An increase in MECP2 dosage impairs neural tube formation.
Published: March, 2014

Abstract: Epigenetic mechanisms are fundamental for shaping the activity of the central nervous system (CNS). Methyl-CpG binding protein 2 (MECP2) acts as a bridge between methylated DNA and transcriptional effectors responsible for differentiation programs...
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Calcium-sensing receptor silencing in colorectal cancer is associated with promoter hypermethylation and loss of acetylation on histone 3.
Published: March, 2014

Abstract: The calcium-sensing receptor (CaSR) is suggested to mediate the antiproliferative effects of calcium in colon. However, in colorectal cancer (CRC) the expression of the CaSR is silenced and the underlying mechanisms leading to its loss are poorly ...
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Immune evasion by oncogenic proteins of acute myeloid leukemia.
Published: March, 2014

Abstract: PML-RARA and AML1-ETO are important oncogenic fusion proteins that play a central role in transformation to acute myeloid leukemia (AML). Whether these fusion proteins render the tumor cells with immune evasion properties is unknown. Here we show ...
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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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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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Principles of nucleation of H3K27 methylation during embryonic development.
Published: March, 2014

Abstract: During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are u...
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Extensive amplification of the E2F transcription factor binding sites by transposons during evolution of Brassica species.
Published: March, 2014

Abstract: Transposable elements (TEs) are major players in genome evolution. The effects of their movement vary from gene knockouts to more subtle effects such as changes in gene expression. It has recently been shown that TEs may contain transcription fact...
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Epigenetics of prostate cancer: distribution of histone H3K27me3 biomarkers in peri-tumoral tissue.
Published: March, 2014

Abstract: Prostate cancer is the second most common cause of cancer and the sixth leading cause of cancer fatalities in men world- wide (Ferlay et al., 2010). Genetic abnormalities and mutations are primary causative factors, but epigenetic mechanisms are n...
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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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Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats.
Published: March, 2014

Abstract: Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life exposures to low doses of BPA exert long-lasting effects on animals' reproductive and brain physiology. However, little is known about the effects of BPA on the stress-resp...
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Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons.
Published: February, 2014

Abstract: The disease mechanism of Rett syndrome (RTT) is not well understood. Studies in RTT mouse models have suggested a non-cell-autonomous role for astrocytes in RTT pathogenesis. However, it is not clear whether this is also true for human RTT astrocy...
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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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Pharmacological inhibition of EZH2 as a promising differentiation therapy in embryonal RMS
Published: February, 2014

Abstract: Background Embryonal Rhabdomyosarcoma (RMS) is a pediatric soft-tissue sarcoma derived from myogenic precursors that is characterized by a good prognosis in patients with localized disease. Conversely, metastatic tumors often relapse, leading to...
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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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Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring.
Published: February, 2014

Abstract: The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offsprin...
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A novel microscopy-based high-throughput screening method to identify proteins that regulate global histone modification levels.
Published: February, 2014

Abstract: Posttranslational modifications of histones play an important role in the regulation of gene expression and chromatin structure in eukaryotes. The balance between chromatin factors depositing (writers) and removing (erasers) histone marks regulate...
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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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Increased binding of MeCP2 to the GAD1 and RELN promoters may be mediated by an enrichment of 5-hmC in autism spectrum disorder (ASD) cerebellum.
Published: January, 2014

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by symptoms related to altered social interactions/communication and restricted and repetitive behaviors. In addition to genetic risk, epigenetic mechanisms (which inclu...
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SUPT6H controls estrogen receptor activity and cellular differentiation by multiple epigenomic mechanisms.
Published: January, 2014

Abstract: The estrogen receptor alpha (ERα) is the central transcriptional regulator of ductal mammary epithelial lineage specification and is an important prognostic marker in human breast cancer. Although antiestrogen therapies are initially highly effect...
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Alterations of epigenetic signatures in hepatocyte nuclear factor 4α deficient mouse liver determined by improved ChIP-qPCR and (h)MeDIP-qPCR assays.
Published: January, 2014

Abstract: Hepatocyte nuclear factor 4α (HNF4α) is a liver-enriched transcription factor essential for liver development and function. In hepatocytes, HNF4α regulates a large number of genes important for nutrient/xenobiotic metabolism and cell differentiati...
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Peroxisome proliferator-activated receptor γ regulates genes involved in insulin/insulin-like growth factor signaling and lipid metabolism during adipogenesis through functionally distinct enhancer classes.
Published: January, 2014

Abstract: The nuclear receptor peroxisome proliferator-activated receptor (PPAR) is a transcription factor whose expression is induced during adipogenesis and that is required for the acquisition and control of mature adipocyte functions. Indeed, PPAR induc...
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Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.
Published: January, 2014

Abstract: In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling...
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Quiescent hepatic stellate cells functionally contribute to the hepatic innate immune response via TLR3.
Published: January, 2014

Abstract: Toll-like Receptor 3 (TLR3) is a pathogen pattern recognition receptor that plays a key role in innate immunity. TLR3 signalling has numerous functions in liver, both in health and disease. Here we report that TLR3 is expressed by quiescent hepati...
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Hypermethylation of the alternative AWT1 promoter in hematological malignancies is a highly specific marker for acute myeloid leukemias despite high expression levels.
Published: January, 2014

Abstract: BACKGROUND: Wilms tumor 1 (WT1) is over-expressed in numerous cancers with respect to normal cells, and has either a tumor suppressor or oncogenic role depending on cellular context. This gene is associated with numerous alternatively spliced tran...
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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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HDAC inhibitor confers radiosensitivity to prostate stem-like cells.
Published: December, 2013

Abstract: Background:Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant frac...
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ZRF1 controls the retinoic acid pathway and regulates leukemogenic potential in acute myeloid leukemia.
Published: December, 2013

Abstract: Acute myeloid leukemia (AML) is frequently linked to epigenetic abnormalities and deregulation of gene transcription, which lead to aberrant cell proliferation and accumulation of undifferentiated precursors. ZRF1, a recently characterized epigene...
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Genome-wide analysis of DNA methylation changes induced by gestational arsenic exposure in liver tumors.
Published: December, 2013

Abstract: Inorganic arsenic is known to be a human carcinogen. Previous studies have reported that DNA methylation changes are involved in arsenic-induced carcinogenesis, therefore, DNA methylation changes that are specific to arsenic-induced tumors would b...
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A key role for EZH2 in epigenetic silencing of HOX genes in mantle cell lymphoma.
Published: December, 2013

Abstract: The chromatin modifier EZH2 is overexpressed and associated with inferior outcome in mantle cell lymphoma (MCL). Recently, we demonstrated preferential DNA methylation of HOX genes in MCL compared with chronic lymphocytic leukemia (CLL), despite t...
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Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood.
Published: December, 2013

Abstract: Individuals carrying (GGGGCC) expanded repeats in the C9orf72 gene represent a significant portion of patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Elucidating how these expanded repeats cause "c9FT...
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Promoter Hypomethylation of EpCAM-Regulated Bone Morphogenetic Protein Gene Family in Recurrent Endometrial Cancer.
Published: November, 2013

Abstract: PURPOSE: Epigenetic regulation by promoter methylation plays a key role in tumorigenesis. Our goal was to investigate whether altered DNA methylation signatures associated with oncogenic signaling delineate biomarkers predictive of endometrial can...
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The polycomb protein Ezh2 regulates differentiation and plasticity of CD4(+) T helper type 1 and type 2 cells.
Published: November, 2013

Abstract: After antigen encounter by CD4(+) T cells, polarizing cytokines induce the expression of master regulators that control differentiation. Inactivation of the histone methyltransferase Ezh2 was found to specifically enhance T helper 1 (Th1) and Th2 ...
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Dynamic reprogramming of 5-hydroxymethylcytosine during early porcine embryogenesis.
Published: November, 2013

Abstract: DNA active demethylation is an important epigenetic phenomenon observed in porcine zygotes, yet its molecular origins are unknown. Our results show that 5-methylcytosine (5mC) converts into 5-hydroxymethylcytosine (5hmC) during the first cell cycl...
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Dynamic CCAAT/Enhancer Binding Protein-Associated Changes of DNA Methylation in the Angiotensinogen Gene.
Published: November, 2013

Abstract: DNA methylation patterns are maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not preserved. We demonstrate that stimulatory signals can change the DNA methylation status at a CCAAT/enhancer bi...
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Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: Increased HSP70-glucocorticoid receptor heterocomplex.
Published: November, 2013

Abstract: Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate G...
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Live visualization of chromatin dynamics with fluorescent TALEs.
Published: November, 2013

Abstract: The spatiotemporal organization of genomes in the nucleus is an emerging key player to regulate genome function. Live imaging of nuclear organization dynamics would be a breakthrough toward uncovering the functional relevance and mechanisms regula...
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Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.
Published: November, 2013

Abstract: DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di-...
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The Elongin Complex Antagonizes the Chromatin Factor Corto for Vein versus Intervein Cell Identity in Drosophila Wings.
Published: October, 2013

Abstract: Drosophila wings mainly consist of two cell types, vein and intervein cells. Acquisition of either fate depends on specific expression of genes that are controlled by several signaling pathways. The nuclear mechanisms that translate signaling into...
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Targeted disruption of hotair leads to homeotic transformation and gene derepression.
Published: October, 2013

Abstract: Long noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here, we show that targeted deletion of mouse Hotair lncRNA leads to derepression of h...
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Dimethyl fumarate regulates histone deacetylase expression in astrocytes.
Published: October, 2013

Abstract: We previously showed that dimethyl fumarate (DMF) reduces inflammatory activation in astrocytes, involving activation of transcription factor Nrf2. However, the pathways causing Nrf2 activation were not examined. We now show that DMF modifies expr...
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Global DNA methylation screening of liver in piperonyl butoxide-treated mice in a two-stage hepatocarcinogenesis model.
Published: October, 2013

Abstract: Disruptive epigenetic gene control has been shown to be involved in carcinogenesis. To identify key molecules in piperonyl butoxide (PBO)-induced hepatocarcinogenesis, we searched hypermethylated genes using CpG island (CGI) microarrays in non-neo...
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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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Epstein-Barr virus-mediated transformation of B cells induces global chromatin changes independent to the acquisition of proliferation.
Published: October, 2013

Abstract: Epstein-Barr virus (EBV) infects and transforms human primary B cells inducing indefinite proliferation. To investigate the potential participation of chromatin mechanisms during the EBV-mediated transformation of resting B cells we performed an a...
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FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis
Published: October, 2013

Abstract: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It is associated with deletion of a macrosatellite repeat leading to over-expression of the nearby genes. Among them, we focused on...
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The trithorax group proteins Kismet and ASH1 promote H3K36 dimethylation to counteract Polycomb group repression in Drosophila.
Published: October, 2013

Abstract: Members of the Polycomb group of repressors and trithorax group of activators maintain heritable states of transcription by modifying nucleosomal histones or remodeling chromatin. Although tremendous progress has been made toward defining the bioc...
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Genome-wide shRNA screening to identify factors mediating Gata6 repression in mouse embryonic stem cells.
Published: October, 2013

Abstract: The use of whole-genome pooled shRNA libraries in loss-of-function screening in tissue culture models provides an effective means to identify novel factors acting in pathways of interest. Embryonic stem cells (ESCs) offer a unique opportunity to s...
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Transcription termination and chimeric RNA formation controlled by Arabidopsis thaliana FPA.
Published: October, 2013

Abstract: Alternative cleavage and polyadenylation influence the coding and regulatory potential of mRNAs and where transcription termination occurs. Although widespread, few regulators of this process are known. The Arabidopsis thaliana protein FPA is a ra...
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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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Combinatorial functions of diverse histone methylations in Arabidopsis thaliana flowering time regulation.
Published: September, 2013

Abstract: Previous studies in Arabidopsis thaliana have identified several histone methylation enzymes, including ARABIDOPSIS TRITHORAX1 (ATX1)/SET DOMAIN GROUP 27 (SDG27), ATX2/SDG30, LSD1-LIKE1 (LDL1), LDL2, SDG8, SDG25, and CURLY LEAF (CLF)/SDG1, as regu...
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Histone deacetylase complex1 expression level titrates plant growth and abscisic Acid sensitivity in Arabidopsis.
Published: September, 2013

Abstract: Histone deacetylation regulates gene expression during plant stress responses and is therefore an interesting target for epigenetic manipulation of stress sensitivity in plants. Unfortunately, overexpression of the core enzymes (histone deacetylas...
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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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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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An In-Depth Characterization of the Major Psoriasis Susceptibility Locus Identifies Candidate Susceptibility Alleles within an HLA-C Enhancer Element.
Published: August, 2013

Abstract: Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS) have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to...
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Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice.
Published: August, 2013

Abstract: Epigenetic reprogramming of host genes via DNA methylation is increasingly recognized as critical for the outcome of diverse infectious diseases, but information for malaria is not yet available. Here, we investigate the effect of blood-stage mala...
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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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Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
Published: August, 2013

Abstract: DNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germ line, and may be mediated by Tet (ten eleven t...
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VAL- and AtBMI1-Mediated H2Aub Initiate the Switch from Embryonic to Postgerminative Growth in Arabidopsis.
Published: July, 2013

Abstract: Plant B3-domain transcription factors have an important role in regulating seed development, in particular seed maturation and germination [1]. Among the B3 factors, the AFL (ABSCISIC ACID INSENSITIVE3 [ABI3], FUSCA3 [FUS3], and LEAFY COTYLEDON2 [...
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DNA methylation of dermal MSCs in psoriasis: Identification of epigenetically dysregulated genes.
Published: July, 2013

Abstract: BACKGROUND: Mesenchymal stem cells (MSCs) are likely involved in pathological processes of immune-related diseases, including psoriasis, because of their immunoregulatory and pro-angiogenic effects. DNA methylation plays an essential role in regul...
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Imprinted Chromatin around DIRAS3 Regulates Alternative Splicing of GNG12-AS1, a Long Noncoding RNA.
Published: July, 2013

Abstract: Imprinted gene clusters are regulated by long noncoding RNAs (lncRNAs), CCCTC binding factor (CTCF)-mediated boundaries, and DNA methylation. DIRAS3 (also known as ARH1 or NOEY1) is an imprinted gene encoding a protein belonging to the RAS superfa...
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Transgene- and locus-dependent imprinting reveals allele-specific chromosome conformations.
Published: July, 2013

Abstract: When positioned into the integrin α-6 gene, an Hoxd9lacZ reporter transgene displayed parental imprinting in mouse embryos. While the expression from the paternal allele was comparable with patterns seen for the same transgene when present at the ...
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Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.
Published: July, 2013

Abstract: A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic ...
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Passaging Techniques and ROCK Inhibitor Exert Reversible Effects on Morphology and Pluripotency Marker Gene Expression of Human Embryonic Stem Cell Lines.
Published: July, 2013

Abstract: Human embryonic stem cells (hESCs) are known for their potential usage in regenerative medicine, but also for handling sensitivity. Much effort has been put into optimizing the culture methods of hESCs. It has been shown that the use of Rho-associ...
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Progesterone receptor induces bcl-x expression through intragenic binding sites favoring RNA polymerase II elongation.
Published: July, 2013

Abstract: Steroid receptors were classically described for regulating transcription by binding to target gene promoters. However, genome-wide studies reveal that steroid receptors-binding sites are mainly located at intragenic regions. To determine the role...
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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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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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Deciphering the cryptic genome: genome-wide analyses of the rice pathogen Fusarium fujikuroi reveal complex regulation of secondary metabolism and novel metabolites.
Published: June, 2013

Abstract: The fungus Fusarium fujikuroi causes "bakanae" disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and th...
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Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m5C within archaeal mRNAs.
Published: June, 2013

Abstract: The presence of 5-methylcytidine (m(5)C) in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago. However, detection of this modification was limited to specific, abundant, RNA species, due to the usage ...
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Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.
Published: June, 2013

Abstract: Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for...
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Multivalent histone engagement by the linked tandem Tudor and PHD domains of UHRF1 is required for the epigenetic inheritance of DNA methylation.
Published: June, 2013

Abstract: Histone post-translational modifications regulate chromatin structure and function largely through interactions with effector proteins that often contain multiple histone-binding domains. While significant progress has been made characterizing ind...
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Characterization of the DNA methylome and its interindividual variation in human peripheral blood monocytes.
Published: June, 2013

Abstract: AIM: Peripheral blood monocytes (PBMs) play multiple and critical roles in the immune response, and abnormalities in PBMs have been linked to a variety of human disorders. However, the DNA methylation landscape in PBMs is largely unknown. In this ...
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Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer.
Published: May, 2013

Abstract: LINE-1 retrotransposons are abundant repetitive elements of viral origin, which in normal cells are kept quiescent through epigenetic mechanisms. Activation of LINE-1 occurs frequently in cancer and can enable LINE-1 mobilization but also has retr...
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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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Thalamic control of neocortical area formation in mice.
Published: May, 2013

Abstract: The mammalian neocortex undergoes dramatic transformation during development, from a seemingly homogenous sheet of neuroepithelial cells into a complex structure that is tangentially divided into discrete areas. This process is thought to be contr...
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An isoform of retinoid-related orphan receptor β directs differentiation of retinal amacrine and horizontal interneurons.
Published: May, 2013

Abstract: Amacrine and horizontal interneurons integrate visual information as it is relayed through the retina from the photoreceptors to the ganglion cells. The early steps that generate these interneuron networks remain unclear. Here we show that a disti...
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Methyl donor supplementation blocks the adverse effects of maternal high fat diet on offspring physiology.
Published: May, 2013

Abstract: Maternal consumption of a high fat diet during pregnancy increases the offspring risk for obesity. Using a mouse model, we have previously shown that maternal consumption of a high fat (60%) diet leads to global and gene specific decreases in DNA ...
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Liver x receptors protect from development of prostatic intra-epithelial neoplasia in mice.
Published: May, 2013

Abstract: LXR (Liver X Receptors) act as "sensor" proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study show...
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Differential transcript isoform usage pre- and post-zygotic genome activation in zebrafish.
Published: May, 2013

Abstract: BACKGROUND: Zebrafish embryos are transcriptionally silent until activation of the zygotic genome during the 10th cell cycle. Onset of transcription is followed by cellular and morphological changes involving cell speciation and gastrulation. Prev...
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First evidence of DNA methylation in insect Tribolium castaneum: environmental regulation of DNA methylation within heterochromatin.
Published: May, 2013

Abstract: DNA methylation has been studied in many eukaryotic organisms, in particular vertebrates, and was implicated in developmental and phenotypic variations. Little is known about the role of DNA methylation in invertebrates, although insects are consi...
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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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An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1.
Published: April, 2013

Abstract: EZH2 or EZH1 is the catalytic subunit of the polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27). The trimethylation of H3K27 (H3K27me3) is a transcriptionally repressive post-translational modification. Overex...
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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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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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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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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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Naive pluripotency is associated with global DNA hypomethylation.
Published: March, 2013

Abstract: Naive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are derived from the preimplantation epiblast and primordial germ cells (PGCs), respectively. We investigated whether differences exist between ESCs and EGCs, in view of...
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Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis.
Published: February, 2013

Abstract: DNA methylation in mammals is highly dynamic during germ cell and preimplantation development but is relatively static during the development of somatic tissues. 5-hydroxymethylcytosine (5hmC), created by oxidation of 5-methylcytosine (5mC) by Tet...
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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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DNA methylation analysis in the intestinal epithelium-effect of cell separation on gene expression and methylation profile.
Published: February, 2013

Abstract: BACKGROUND: Epigenetic signatures are highly cell type specific. Separation of distinct cell populations is therefore desirable for all epigenetic studies. However, to date little information is available on whether separation protocols might infl...
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DNA methylation mediated control of gene expression is critical for development of crown gall tumors.
Published: February, 2013

Abstract: Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown ga...
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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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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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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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Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations
Published: January, 2013

Abstract: Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritanc...
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Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Obesity, Reproductive Disease and Sperm Epimutations
Published: January, 2013

Abstract: Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1–F3) following ancestral exposure during fetal gonadal sex determination. The current study was designed to d...
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The N-terminal segment of Plasmodium falciparum SURFIN(4.1) is required for its trafficking to the red blood cell cytosol through the endoplasmic reticulum.
Published: December, 2012

Abstract: Plasmodium falciparum SURFIN is a type I transmembrane protein that shares domains with molecules expressed on the surface of the red blood cells (RBCs) infected with a variety of malaria parasite species, such as P. falciparum PfEMP1, P. vivax VI...
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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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MeCP2 Binds to 5hmC Enriched within Active Genes and Accessible Chromatin in the Nervous System.
Published: December, 2012

Abstract: The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, ...
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Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues
Published: December, 2012

Abstract: Aberrant DNA methylation often occurs in colorectal cancer (CRC). In our study we applied a genome-wide DNA methylation analysis approach, MethylCap-seq, to map the differentially methylated regions (DMRs) in 24 tumors and matched normal colon sam...
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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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Ash2 acts as an Ecdysone Receptor coactivator by stabilizing the histone methyltransferase Trr.
Published: November, 2012

Abstract: The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-...
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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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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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Inhibition of Tumor Promotion by Parthenolide: Epigenetic Modulation of p21.
Published: November, 2012

Abstract: The promotion stage in the multistep process of epidermal tumorigenesis is NF-кB-dependent, epigenetically regulated, and reversible, thus, a suitable target for chemoprevention. We investigated whether the NF-кB inhibitor, parthenolide, currently...
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Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons.
Published: October, 2012

Abstract: The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during...
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IL-23 is pro-proliferative, epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer.
Published: October, 2012

Abstract: BACKGROUND: IL-23 is a member of the IL-6 super-family and plays key roles in cancer. Very little is currently known about the role of IL-23 in non-small cell lung cancer (NSCLC). METHODS: RT-PCR and chromatin immunopreciptiation (ChIP) were used ...
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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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Non-genotoxic carcinogen exposure induces defined changes in the 5-hydroxymethylome.
Published: October, 2012

Abstract: ABSTRACT: BACKGROUND: Induction and promotion of liver cancer by exposure to non-genotoxic carcinogens coincides with epigenetic perturbations, including specific changes in DNA methylation. Here we investigate the genome-wide dynamics of 5-hydro...
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Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes.
Published: October, 2012

Abstract: A significant portion of the genome is transcribed as long noncoding RNAs (lncRNAs), several of which are known to control gene expression. The repertoire and regulation of lncRNAs in disease-relevant tissues, however, has not been systematically ...
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Features of the Arabidopsis recombination landscape resulting from the combined loss of sequence variation and DNA methylation.
Published: October, 2012

Abstract: The rate of meiotic crossing over (CO) varies considerably along chromosomes, leading to marked distortions between physical and genetic distances. The causes underlying this variation are being unraveled, and DNA sequence and chromatin states hav...
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Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.
Published: October, 2012

Abstract: The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the ...
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Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation.
Published: September, 2012

Abstract: A fundamental challenge in mammalian biology has been the elucidation of mechanisms linking DNA methylation and histone post-translational modifications. Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has multiple domains tha...
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Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.
Published: September, 2012

Abstract: Adaptive features of innate immunity, recently described as "trained immunity," have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteer...
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p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6.
Published: September, 2012

Abstract: p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting G1 cell cycle arrest and cellular senescence. Consistent with this role, p21 is a downstream target of several tumour suppressors and oncogenes, and it is downregulat...
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ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia.
Published: September, 2012

Abstract: ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here, genome-wide analysis revealed that both ER...
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H4K20me1 Contributes to Downregulation of X-Linked Genes for C. elegans Dosage Compensation
Published: September, 2012

Abstract: The Caenorhabditis elegans dosage compensation complex (DCC) equalizes X-chromosome gene dosage between XO males and XX hermaphrodites by two-fold repression of X-linked gene expression in hermaphrodites. The DCC localizes to the X chromosomes in ...
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Tet2 Facilitates the Derepression of Myeloid Target Genes during CEBPα-Induced Transdifferentiation of Pre-B Cells.
Published: September, 2012

Abstract: The methylcytosine hydroxylase Tet2 has been implicated in hematopoietic differentiation and the formation of myeloid malignancies when mutated. An ideal system to study the role of Tet2 in myelopoeisis is CEBPα-induced transdifferentiation of pre...
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Pesticide and Insect Repellent Mixture (Permethrin and DEET) Induces Epigenetic Transgenerational Inheritance of Disease and Sperm Epimutations.
Published: September, 2012

Abstract: Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a "pesticide mixture" (pesticide permethrin and insect repellent N,N-Diethyl-meta-toluamide, DEET) pro...
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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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Chromatin accessibility, p300 and histone acetylation define PML-RARα and AML1-ETO binding sites in acute myeloid leukemia.
Published: August, 2012

Abstract: Chromatin accessibility plays a key role in regulating cell type specific gene expression during hematopoiesis, but has also been suggested to be aberrantly regulated during leukemogenesis. To understand the leukemogenic chromatin signature we ana...
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Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes.
Published: August, 2012

Abstract: Immunological memory in vertebrates is often exclusively attributed to T and B cell function. Recently it was proposed that the enhanced and sustained innate immune responses following initial infectious exposure may also afford protection against...
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Histone acetylation and DNA demethylation of T-cells result in an anaplastic large cell lymphoma-like phenotype.
Published: August, 2012

Abstract: Background. A characteristic feature of anaplastic large cell lymphoma is the significant repression of the T-cell expression program despite its T-cell origin. The reasons for this down-regulation of T-cell phenotype are still unknown. Design and...
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The Human EKC/KEOPS Complex Is Recruited to Cullin2 Ubiquitin Ligases by the Human Tumour Antigen PRAME.
Published: August, 2012

Abstract: The human tumour antigen PRAME (preferentially expressed antigen in melanoma) is frequently overexpressed during oncogenesis, and high PRAME levels are associated with poor clinical outcome in a variety of cancers. However, the molecular pathways ...
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A Sharp Cadherin-6 Gene Expression Boundary in the Developing Mouse Cortical Plate Demarcates the Future Functional Areal Border.
Published: August, 2012

Abstract: The mammalian cerebral cortex can be tangentially subdivided into tens of functional areas with distinct cyto-architectures and neural circuitries; however, it remains elusive how these areal borders are genetically elaborated during development. ...
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Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase I transcription.
Published: August, 2012

Abstract: Nucleolin is a multi-functional nucleolar protein that is required for ribosomal RNA gene (rRNA) transcription in vivo, but the mechanism by which nucleolin modulates RNA polymerase I (RNAPI) transcription is not well understood. Nucleolin depleti...
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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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The H3K4me3 histone demethylase Fbxl10 is a regulator of chemokine expression, cellular morphology and the metabolome of fibroblasts
Published: July, 2012

Abstract: Fbxl10 (Jhdm1b/Kdm2b) is a conserved and ubiquitously expressed member of the JHDM (JmjC-domain-containing histone demethy-lase) family. Fbxl10 was implicated in the demethylation of H3K4me3 or H3K36me2 thereby removing active chromatin marks and ...
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A comparison of transcriptome and epigenetic status between closely related species in the genus Arabidopsis.
Published: July, 2012

Abstract: Difference in the level of expression of genes is one of the factors contributing to plant phenotype. As well as being under genetic control, gene expression is regulated by epigenetic processes such as DNA methylation and histone modifications. W...
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Dynamic Changes in Ezh2 Gene Occupancy Underlie Its Involvement in Neural Stem Cell Self-Renewal and Differentiation towards Oligodendrocytes
Published: July, 2012

Abstract: Background: The polycomb group protein Ezh2 is an epigenetic repressor of transcription originally found to prevent untimely differentiation of pluripotent embryonic stem cells. We previously demonstrated that Ezh2 is also expressed in multipotent...
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An essential novel component of the non-canonical mitochondrial outer membrane protein import system of trypanosomatids.
Published: July, 2012

Abstract: The mitochondrial outer membrane protein Tom40 is the general entry gate for imported proteins in essentially all eukaryotes. Trypanosomatids however lack Tom40 and use instead a protein termed the archaic translocase of the outer mitochondrial me...
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Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers.
Published: June, 2012

Abstract: Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyri...
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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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Identification of PR-SET7 and EZH2 selective inhibitors inducing cell death in human leukemia U937 cells.
Published: June, 2012

Abstract: Chemical manipulations undertaken on some bis(bromo- and dibromo-phenol) compounds previously reported by us as wide-spectrum epigenetic inhibitors let us to identify bis (bromo- and dibromo-methoxyphenyl) derivatives highly selective for PR-SET7 ...
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Genome-Wide DNA Methylation Changes between the Superficial and Deep Backfat Tissues of the Pig
Published: June, 2012

Abstract:
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Phosphorylation of p65(RelA) on Ser547 by ATM Represses NF-κB-Dependent Transcription of Specific Genes after Genotoxic Stress
Published: June, 2012

Abstract:
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The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells.
Published: June, 2012

Abstract: Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their func...
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Genome-wide localization and expression profiling establish Sp2 as a sequence-specific transcription factor regulating vitally important genes.
Published: June, 2012

Abstract: The transcription factor Sp2 is essential for early mouse development and for proliferation of mouse embryonic fibroblasts in culture. Yet its mechanisms of action and its target genes are largely unknown. In this study, we have combined RNA inter...
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Recruitment of histone deacetylase 3 to the interferon-a gene promoters attenuates interferon expression.
Published: June, 2012

Abstract: BACKGROUND: Induction of Type I Interferon (IFN) genes constitutes an essential step leading to innate immune responses during virus infection. Sendai virus (SeV) infection of B lymphoid Namalwa cells transiently induces the transcriptional expres...
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Intronic RNAs mediate EZH2 regulation of epigenetic targets.
Published: June, 2012

Abstract: Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking ...
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Design, Synthesis, and Biological Evaluation of 2-Aminobenzanilide Derivatives as Potent and Selective HDAC Inhibitors.
Published: May, 2012

Abstract: Epigenetic regulation is an essential process for the normal functioning of genes. Therefore, targeting epigenetic dysregulation in cancer may be a valid therapeutic approach for the treatment of this severe disease. Histone deacetylases (HDACs) a...
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Lysine-specific demethylase 1 (LSD1) and histone deacetylase 1 (HDAC1) synergistically repress proinflammatory cytokines and classical complement pathway components
Published: May, 2012

Abstract:
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Epigenetic Repression of RARRES1 Is Mediated by Methylation of a Proximal Promoter and a Loss of CTCF Binding.
Published: May, 2012

Abstract: BACKGROUND: The cis-acting promoter element responsible for epigenetic silencing of retinoic acid receptor responder 1 (RARRES1) by methylation is unclear. Likewise, how aberrant methylation interplays effectors and thus affects breast neoplastic ...
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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 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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DNA methylation in an intron of the IBM1 histone demethylase gene stabilizes chromatin modification patterns.
Published: May, 2012

Abstract: The stability of epigenetic patterns is critical for genome integrity and gene expression. This highly coordinated process involves interrelated positive and negative regulators that impact distinct epigenetic marks, including DNA methylation and ...
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Environmentally induced epigenetic transgenerational inheritance of ovarian disease.
Published: May, 2012

Abstract: The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbo...
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Lxrα Regulates the Androgen Response in Prostate Epithelium.
Published: April, 2012

Abstract: Benign prostatic hyperplasia is a nonmalignant enlargement of the prostate that commonly occurs in older men. We show that liver X receptor (Lxr)-α knockout mice (lxrα(-/-)) develop ventral prostate hypertrophy, correlating with an overaccumulatio...
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Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice.
Published: April, 2012

Abstract: Human studies suggest that a variety of prenatal stressors are related to high risk for cognitive and behavioral abnormalities associated with psychiatric illness (Markham and Koenig, 2011). Recently, a downregulation in the expression of GABAergi...
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The transcriptional and epigenomic foundations of ground state pluripotency.
Published: April, 2012

Abstract: Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" pos...
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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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Breast Cancer Cells Induce Stromal Fibroblasts to Secrete ADAMTS1 for Cancer Invasion through an Epigenetic Change.
Published: April, 2012

Abstract: Microenvironment plays an important role in cancer development. We have reported that the cancer-associated stromal cells exhibit phenotypic and functional changes compared to stromal cells neighboring to normal tissues. However, the molecular mec...
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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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The histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation.
Published: April, 2012

Abstract: BACKGROUND AND AIMS: Transdifferentiation of hepatic stellate cells (HSCs) to a myofibroblast-like phenotype is a pivotal event that drives liver fibrosis. HSC transdifferentiation requires coordinated global changes in gene expression. Here we ha...
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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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C/EBPβ and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2α as the inducer in chondrocytes.
Published: March, 2012

Abstract: To elucidate the molecular mechanism underlying the endochondral ossification process during the skeletal growth and osteoarthritis (OA) development, we examined the signal network around CCAAT/enhancer-binding protein-β (C/EBPβ, encoded by CEBPB)...
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Chromatin structural changes around satellite repeats on the female sex chromosome in Schistosoma mansoni and their possible role in sex chromosome emergence.
Published: February, 2012

Abstract: BACKGROUND: In the leuphotrochozoan parasitic platyhelminth Schistosoma mansoni, male individuals are homogametic (ZZ) whereas females are heterogametic (ZW). To elucidate the mechanisms that led to the emergence of sex chromosomes, we compared th...
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Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures.
Published: February, 2012

Abstract: Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epi...
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The Origin and Nature of Tightly Clustered BTG1 Deletions in Precursor B-Cell Acute Lymphoblastic Leukemia Support a Model of Multiclonal Evolution
Published: February, 2012

Abstract:
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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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Control of ground-state pluripotency by allelic regulation of Nanog.
Published: February, 2012

Abstract: Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of plur...
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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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Heritable genome-wide variation of gene expression and promoter methylation between wild and domesticated chickens.
Published: February, 2012

Abstract: ABSTRACT: BACKGROUND: Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns ...
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Heritable transmission of diabetic metabolic memory in zebrafish correlates with DNA hypomethylation and aberrant gene expression.
Published: February, 2012

Abstract: Metabolic memory (MM) is the phenomenon whereby diabetes complications persist and progress after glycemic recovery is achieved. Here, we present data showing that MM is heritable and that the transmission correlates with hyperglycemia-induced DNA...
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Transcription and histone methylation changes correlate with imprint acquisition in male germ cells.
Published: February, 2012

Abstract: Genomic imprinting in mammals is controlled by DNA methylation imprints that are acquired in the gametes, at essential sequence elements called 'imprinting control regions' (ICRs). What signals paternal imprint acquisition in male germ cells remai...
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Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.
Published: February, 2012

Abstract: While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic ...
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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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Molecular analysis of enhancer RNAs and chromatin modifications in the region of their synthesis in Drosophila cells possessing genetic constructs.
Published: February, 2012

Abstract:
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Dynamic DNA cytosine methylation in the Populus trichocarpa genome: tissue-level variation and relationship to gene expression.
Published: January, 2012

Abstract: ABSTRACT: BACKGROUND: DNA cytosine methylation is an epigenetic modification that has been implicated in many biological processes. However, large-scale epigenomic studies have been applied to very few plant species, and variability in methylatio...
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Growth Arrest and DNA-Damage-Inducible, Beta (GADD45b)-Mediated DNA Demethylation in Major Psychosis.
Published: January, 2012

Abstract: Aberrant neocortical DNA methylation has been suggested to be a pathophysiological contributor to psychotic disorders. Recently, a growth arrest and DNA-damage-inducible, beta (GADD45b) protein-coordinated DNA demethylation pathway, utilizing cyti...
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Novel transcriptional targets of the SRY-HMG box transcription factor SOX4 link its expression to the development of small cell lung cancer.
Published: January, 2012

Abstract: The HMG box transcription factor SOX4 involved in neuronal development is amplified and overexpressed in a subset of lung cancers, suggesting that it may be a driver oncogene. In this study, we sought to develop this hypothesis including by defini...
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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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Prepatterning of developmental gene expression by modified histones before zygotic genome activation.
Published: December, 2011

Abstract: A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes...
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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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Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study.
Published: December, 2011

Abstract: BACKGROUND: Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cel...
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Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation.
Published: December, 2011

Abstract: Ten-eleven translocation 1-3 (Tet1-3) proteins have recently been discovered in mammalian cells to be members of a family of DNA hydroxylases that possess enzymatic activity toward the methyl mark on the 5-position of cytosine (5-methylcytosine [5...
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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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Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes.
Published: November, 2011

Abstract: Transcription factor-induced lineage reprogramming or transdifferentiation experiments are essential for understanding the plasticity of differentiated cells. These experiments helped to define the specific role of transcription factors in conferr...
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Bivalent histone modifications in stem cells poise miRNA loci for CpG island hypermethylation in human cancer.
Published: November, 2011

Abstract: It has been proposed that the existence of stem cell epigenetic patterns confer a greater likelihood of CpG island hypermethylation on tumor suppressor-coding genes in cancer. The suggested mechanism is based on the Polycomb-mediated methylation o...
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PcG complexes set the stage for epigenetic inheritance of gene silencing in early S phase before replication.
Published: November, 2011

Abstract: Polycomb group (PcG) proteins are part of a conserved cell memory system that conveys epigenetic inheritance of silenced transcriptional states through cell division. Despite the considerable amount of information about PcG mechanisms controlling ...
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CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
Published: October, 2011

Abstract: Alternative splicing of pre-messenger RNA is a key feature of transcriptome expansion in eukaryotic cells, yet its regulation is poorly understood. Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may di...
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The human histone H3 complement anno 2011.
Published: October, 2011

Abstract: Histones are highly basic, relatively small proteins that complex with DNA to form higher order structures that underlie chromosome topology. Of the four core histones H2A, H2B, H3 and H4, it is H3 that is most heavily modified at the post-transla...
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DNA methylation profiles of human active and inactive X chromosomes.
Published: October, 2011

Abstract: X-chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell. To characterize epigenetic changes that accompany this process, we measured DNA methylation levels in 4...
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Histone tail acetylation in brain occurs in an unpredictable fashion after death.
Published: September, 2011

Abstract: Histone acetylation plays a role in the regulation of gene transcription. Yet it is not known whether post-mortem brain tissue is suitable for the analysis of histone acetylation. To examine this question, nucleosomes were isolated from frontal co...
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Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation.
Published: September, 2011

Abstract: In developing amniote embryos, the first epithelial-to-mesenchymal transition (EMT) occurs at gastrulation, when a subset of epiblast cells moves to the primitive streak and undergoes EMT to internalize and generate the mesoderm and the endoderm. ...
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Glutathione-S-transferase pi 1(GSTP1) gene silencing in prostate cancer cells is reversed by the histone deacetylase inhibitor depsipeptide.
Published: September, 2011

Abstract: Gene silencing by epigenetic mechanisms is frequent in prostate cancer (PCA). The link between DNA hypermethylation and histone modifications is not completely understood. We chose the GSTP1 gene which is silenced by hypermethylation to analyze th...
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Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer.
Published: September, 2011

Abstract: The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-i...
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Disruption of the histone acetyltransferase MYST4 leads to a Noonan syndrome-like phenotype and hyperactivated MAPK signaling in humans and mice.
Published: September, 2011

Abstract: Epigenetic regulation of gene expression, through covalent modification of histones, is a key process controlling growth and development. Accordingly, the transcription factors regulating these processes are important targets of genetic diseases. ...
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Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development.
Published: September, 2011

Abstract: Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered. Here we examine 5-hmC distribution during mammalian development and in cel...
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Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.
Published: September, 2011

Abstract: Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolate...
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Coactivation of GR and NFKB alters the repertoire of their binding sites and target genes.
Published: September, 2011

Abstract: Glucocorticoid receptor (GR) exerts anti-inflammatory action in part by antagonizing proinflammatory transcription factors such as the nuclear factor kappa-b (NFKB). Here, we assess the crosstalk of activated GR and RELA (p65, major NFKB component...
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Selective autophagy regulates insertional mutagenesis by the Ty1 retrotransposon in Saccharomyces cerevisiae.
Published: August, 2011

Abstract: Macroautophagy (autophagy) is a bulk degradation system for cytoplasmic components and is ubiquitously found in eukaryotic cells. Autophagy is induced under starvation conditions and plays a cytoprotective role by degrading unwanted cytoplasmic ma...
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The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters.
Published: August, 2011

Abstract: The human tumour antigen PRAME (preferentially expressed antigen of melanoma) is frequently overexpressed in tumours. High PRAME levels correlate with poor clinical outcome of several cancers, but the mechanisms by which PRAME could be involved in...
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IL-20 is epigenetically regulated in NSCLC and down regulates the expression of VEGF.
Published: August, 2011

Abstract: BACKGROUND: IL-20 is a pleiotrophic member of the IL-10 family and plays a role in skin biology and the development of haematopoietic cells. Recently, IL-20 has been demonstrated to have potential anti-angiogenic effects in non-small cell lung can...
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Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters.
Published: August, 2011

Abstract: Recent work has shown that RNA polymerase (Pol) II can be recruited to and transcribe distal regulatory regions. Here we analyzed transcription initiation and elongation through genome-wide localization of Pol II, general transcription factors (GT...
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5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells.
Published: June, 2011

Abstract: BACKGROUND: 5-Hydroxymethylcytosine (5hmC) was recently found to be abundantly present in certain cell types, including embryonic stem cells. There is growing evidence that TET proteins, which convert 5-methylcytosine (5mC) to 5hmC, play important...
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Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction.
Published: June, 2011

Abstract: Epigenetic fields for cancerization are involved in development of human cancers, especially those associated with inflammation and multiple occurrences. However, it is still unclear when such field defects are formed and what component of inflamm...
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Enhancer of Zeste 2 (EZH2) is up-regulated in malignant gliomas and in glioma stem-like cells.
Published: June, 2011

Abstract: AIMS: Proteins of the Polycomb repressive complex 2 (PRC2) are epigenetic gene silencers and are involved in tumour development. Their oncogenic function might be associated with their role in stem cell maintenance. The histone methyltransferase E...
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LSD1 regulates the balance between self-renewal and differentiation in human embryonic stem cells.
Published: June, 2011

Abstract: We identify LSD1 (lysine-specific demethylase 1; also known as KDM1A and AOF2) as a key histone modifier that participates in the maintenance of pluripotency through the regulation of bivalent domains, a chromatin environment present at the regula...
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H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes.
Published: June, 2011

Abstract: The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specif...
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Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells.
Published: May, 2011

Abstract: Methylation of histone H3 lysine 4 (H3K4me), a mark associated with gene activation, is mediated by SET1 and the related mixed lineage leukemia (MLL) histone methyltransferases (HMTs) across species. Mammals contain seven H3K4 HMTs, Set1A, Set1B, ...
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Epigenetic profile of the euchromatic region of human Y chromosome.
Published: May, 2011

Abstract: The genome of a multi-cellular organism acquires various functional capabilities in different cell types by means of distinct chromatin modifications and packaging states. Acquired during early development, the cell type-specific epigenotype is ma...
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Regulation of mouse embryonic stem cell self-renewal by a Yes-YAP-TEAD2 signaling pathway downstream of LIF.
Published: April, 2011

Abstract: The cytoplasmic tyrosine kinase Yes has previously been shown to have an important role in maintaining mouse and human embryonic stem (ES) self-renewal through an unknown pathway downstream of leukemia inhibitory factor (LIF) and one or more facto...
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Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers.
Published: April, 2011

Abstract: Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis-regulatory elements. Among those are enhancers, which play key roles in regulation of gene expression during development and differentiation. Despite...
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Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells.
Published: April, 2011

Abstract: Recent studies have demonstrated that the Ten-eleven translocation (Tet) family proteins can enzymatically convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). While 5mC has been studied extensively, little is known about the distribu...
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Recombineering, transfection, Western, IP and ChIP methods for protein tagging via gene targeting or BAC transgenesis.
Published: April, 2011

Abstract: Protein tagging offers many advantages for proteomic and regulomic research. Ideally, protein tagging is equivalent to having a high affinity antibody for every chosen protein. However, these advantages are compromised if the tagged protein is ove...
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Epigenetic Regulation of Glucose Transporters in Non-Small Cell Lung Cancer
Published: March, 2011

Abstract: Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin...
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5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming.
Published: March, 2011

Abstract: The epigenomes of early mammalian embryos are extensively reprogrammed to acquire a totipotent developmental potential. A major initial event in this reprogramming is the active loss/demethylation of 5-methylcytosine (5mC) in the zygote. Here, we ...
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Epigenetic silencing mediated through activated PI3K/AKT signaling in breast cancer.
Published: March, 2011

Abstract: Trimethylation of histone 3 lysine 27 (H3K27me3) is a critical epigenetic mark for the maintenance of gene silencing. Additional accumulation of DNA methylation in target loci is thought to cooperatively support this epigenetic silencing during tu...
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Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability.
Published: February, 2011

Abstract: Thymine DNA glycosylase (TDG) is a member of the uracil DNA glycosylase (UDG) superfamily of DNA repair enzymes. Owing to its ability to excise thymine when mispaired with guanine, it was proposed to act against the mutability of 5-methylcytosine ...
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Characterization of the contradictory chromatin signatures at the 3' exons of zinc finger genes.
Published: February, 2011

Abstract: The H3K9me3 histone modification is often found at promoter regions, where it functions to repress transcription. However, we have previously shown that 3' exons of zinc finger genes (ZNFs) are marked by high levels of H3K9me3. We have now further...
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Epigenetic control of vascular smooth muscle cells in Marfan and non-Marfan thoracic aortic aneurysms.
Published: February, 2011

Abstract: AIMS: Human thoracic aortic aneurysms (TAAs) are characterized by extracellular matrix breakdown associated with progressive smooth muscle cell (SMC) rarefaction. These features are present in all types of TAA: monogenic forms [mainly Marfan syndr...
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Comprehensive analysis of DNA-methylation in mammalian tissues using MeDIP-chip.
Published: February, 2011

Abstract: Genome-wide mapping of epigenetic changes is essential for understanding the mechanisms involved in gene regulation during cell differentiation and embryonic development. DNA-methylation is one of these key epigenetic marks that is directly linked...
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The histone methyltransferase Dot1 is required for DNA damage repair and proper development in Dictyostelium.
Published: January, 2011

Abstract: Posttranslational histone modifications play an important role in modulating gene expression and chromatin structure. Here we report the identification of histone H3K79 dimethylation in the simple eukaryote Dictyostelium discoideum. We have delete...
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Inhibition of suppressive T cell factor 1 (TCF-1) isoforms in naive CD4+ T cells is mediated by IL-4/STAT6 signaling.
Published: January, 2011

Abstract: The Wnt pathway transcription factor T cell factor 1 (TCF-1) plays essential roles in the control of several developmental processes, including T cell development in the thymus. Although previously regarded as being required only during early T ce...
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Characterisation of genome-wide PLZF/RARA target genes.
Published: January, 2011

Abstract: The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming...
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Role of p53 serine 46 in p53 target gene regulation.
Published: January, 2011

Abstract: The tumor suppressor p53 plays a crucial role in cellular growth control inducing a plethora of different response pathways. The molecular mechanisms that discriminate between the distinct p53-responses have remained largely elusive. Here, we have...
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Enhanced chromatin accessibility and recruitment of JUNB mediate the sustained IL-4 expression in NFAT1 deficient T helper 2 cells.
Published: January, 2011

Abstract: Nuclear factor of activated T cells (NFAT) is a family of transcription factors composed of five proteins. Among them, NFAT1 is a predominant NFAT protein in CD4(+) T cells. NFAT1 positively regulates transcription of a large number of inducible c...
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Microplate-based platform for combined chromatin and DNA methylation immunoprecipitation assays.
Published: January, 2011

Abstract: UNLABELLED: ABSTRACT: BACKGROUND: The processes that compose expression of a given gene are far more complex than previously thought presenting unprecedented conceptual and mechanistic challenges that require development of new tools. Chromatin st...
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Epigenetic regulation of miR-212 expression in lung cancer.
Published: January, 2011

Abstract: Many studies have shown that microRNA expression in cancer may be regulated by epigenetic events. Recently, we found that in lung cancer miR-212 was strongly down-regulated. However, mechanisms involved in the regulation of miR-212 expression are ...
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Epigenetic activation of SOX11 in lymphoid neoplasms by histone modifications.
Published: January, 2011

Abstract: Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in ...
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Epigenetic regulation on the 5'-proximal CpG island of human porcine endogenous retrovirus subgroup A receptor 2/GPR172B.
Published: January, 2011

Abstract: Porcine endogenous retroviruses (PERVs) have been considered one of the major risks of xenotransplantation from pigs to humans. PERV-A efficiently utilizes human PERV-A receptor 2 (HuPAR-2)/GPR172B to infect human cells; however, there has been no...
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Tiling histone H3 lysine 4 and 27 methylation in zebrafish using high-density microarrays.
Published: December, 2010

Abstract: BACKGROUND: Uncovering epigenetic states by chromatin immunoprecipitation and microarray hybridization (ChIP-chip) has significantly contributed to the understanding of gene regulation at the genome-scale level. Many studies have been carried out ...
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H2A.Z demarcates intergenic regions of the plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3.
Published: December, 2010

Abstract: Epigenetic regulatory mechanisms and their enzymes are promising targets for malaria therapeutic intervention; however, the epigenetic component of gene expression in P. falciparum is poorly understood. Dynamic or stable association of epigenetic ...
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Histone H2A C-terminus regulates chromatin dynamics, remodeling, and histone H1 binding.
Published: December, 2010

Abstract: The tails of histone proteins are central players for all chromatin-mediated processes. Whereas the N-terminal histone tails have been studied extensively, little is known about the function of the H2A C-terminus. Here, we show that the H2A C-term...
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ZNF274 recruits the histone methyltransferase SETDB1 to the 3' ends of ZNF genes.
Published: December, 2010

Abstract: Only a small percentage of human transcription factors (e.g. those associated with a specific differentiation program) are expressed in a given cell type. Thus, cell fate is mainly determined by cell type-specific silencing of transcription factor...
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Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3.
Published: December, 2010

Abstract: The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(...
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STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Published: November, 2010

Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory mili...
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A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.
Published: November, 2010

Abstract: Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system using in...
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Histone modifications at the blastocyst Axin1(Fu) locus mark the heritability of in vitro culture-induced epigenetic alterations in mice.
Published: November, 2010

Abstract: For epigenetic phenotypes to be passed on from one generation to the next, it is required that epigenetic marks between generations are not cleared during the two stages of epigenetic reprogramming: mammalian gametogenesis and preimplantation deve...
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The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells.
Published: November, 2010

Abstract: The initiation of DNA synthesis is governed by the licensing of replication origins, which consists of assembling a pre-replication complex (pre-RC) on origins during late M- and G1-phases. In metazoans, functional replication origins do not show ...
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Promoter-exon relationship of H3 lysine 9, 27, 36 and 79 methylation on pluripotency-associated genes.
Published: October, 2010

Abstract: Evidence links pluripotency to a gene regulatory network organized by the transcription factors Oct4, Nanog and Sox2. Expression of these genes is controlled by epigenetic modifications on regulatory regions. However, little is known on profiles o...
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TNF/p38α/polycomb signaling to Pax7 locus in satellite cells links inflammation to the epigenetic control of muscle regeneration.
Published: October, 2010

Abstract: How regeneration cues are converted into the epigenetic information that controls gene expression in adult stem cells is currently unknown. We identified an inflammation-activated signaling in muscle stem (satellite) cells, by which the polycomb r...
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Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15.
Published: September, 2010

Abstract: The maternal and paternal genomes possess distinct epigenetic marks that distinguish them at imprinted loci. In order to identify imprinted loci, we used a novel method, taking advantage of the fact that uniparental disomy (UPD) provides a system ...
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Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment.
Published: August, 2010

Abstract: Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, the trophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry biv...
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The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats
Published: July, 2010

Abstract: Maintenance of specific heterochromatic domains is crucial for genome stability. In eukaryotic cells, a fraction of the tandem-repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA si...
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ESCs require PRC2 to direct the successful reprogramming of differentiated cells toward pluripotency.
Published: June, 2010

Abstract: Embryonic stem cells (ESCs) are pluripotent, self-renewing, and have the ability to reprogram differentiated cell types to pluripotency upon cellular fusion. Polycomb-group (PcG) proteins are important for restraining the inappropriate expression ...
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Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping.
Published: June, 2010

Abstract: The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-rang...
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det1-1-induced UV-C hyposensitivity through UVR3 and PHR1 photolyase gene over-expression.
Published: May, 2010

Abstract: Summary Obligate photoautotrophs such as plants must capture energy from sunlight and are therefore exposed to the damaging collateral effects of ultraviolet (UV) irradiation, especially on DNA. Here we investigated the interconnection between lig...
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Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4.
Published: April, 2010

Abstract: Demethylation at distinct lysine residues in histone H3 by lysine-specific demethylase 1 (LSD1) causes either gene repression or activation. As a component of co-repressor complexes, LSD1 contributes to target gene repression by removing mono- and...
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A chromodomain switch mediated by histone H3 Lys 4 acetylation regulates heterochromatin assembly.
Published: April, 2010

Abstract: Chromodomain proteins (Chp1/Chp2/Swi6/Clr4) bind to methylated H3K9 (H3K9me) and regulate pericentric heterochromatin in fission yeast. Chp1 and Clr4 (H3K9-HMT), bind transcriptionally active heterochromatin, whereas Chp2/Swi6 (HP1 homologs) are r...
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Autonomous silencing of the imprinted Cdkn1c gene in stem cells
Published: April, 2010

Abstract: Parent-of-origin specific expression of imprinted genes relies on the differential DNA methylation of specific genomic regions. Differentially methylated regions (DMRs) acquire DNA methylation either during gametogenesis (primary DMR) or after fer...
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Alternative splicing of the histone demethylase LSD1/KDM1 contributes to the modulation of neurite morphogenesis in the mammalian nervous system.
Published: February, 2010

Abstract: A variety of chromatin remodeling complexes are thought to orchestrate transcriptional programs that lead neuronal precursors from earliest commitment to terminal differentiation. Here we show that mammalian neurons have a specialized chromatin re...
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PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia.
Published: February, 2010

Abstract: Many different molecular mechanisms have been associated with PML-RARalpha-dependent transformation of hematopoietic progenitors. Here, we identified high confidence PML-RARalpha binding sites in an acute promyelocytic leukemia (APL) cell line and...
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Chromatin remodeling by imitation switch (ISWI) class ATP-dependent remodelers is stimulated by histone variant H2A.Z.
Published: February, 2010

Abstract: ATP-dependent chromatin remodeling complexes rearrange nucleosomes by altering the position of DNA around the histone octamer. Although chromatin remodelers and the histone variant H2A.Z colocalize on transcriptional control regions, whether H2A.Z...
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AGRONOMICS1: a new resource for Arabidopsis transcriptome profiling.
Published: February, 2010

Abstract: Transcriptome profiling has become a routine tool in biology. For Arabidopsis (Arabidopsis thaliana), the Affymetrix ATH1 expression array is most commonly used, but it lacks about one-third of all annotated genes present in the reference strain. ...
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Genome-wide analysis of aberrant methylation in human breast cancer cells using methyl-DNA immunoprecipitation combined with high-throughput sequencing.
Published: January, 2010

Abstract: BACKGROUND: Cancer cells undergo massive alterations to their DNA methylation patterns that result in aberrant gene expression and malignant phenotypes. However, the mechanisms that underlie methylome changes are not well understood nor is the gen...
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The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.
Published: January, 2010

Abstract: Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis o...
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In vivo chromatin organization of mouse rod photoreceptors correlates with histone modifications.
Published: January, 2010

Abstract: BACKGROUND: The folding of genetic information into chromatin plays important regulatory roles in many nuclear processes and particularly in gene transcription. Post translational histone modifications are associated with specific chromatin conden...
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The core binding factor CBF negatively regulates skeletal muscle terminal differentiation.
Published: January, 2010

Abstract: BACKGROUND: Core Binding Factor or CBF is a transcription factor composed of two subunits, Runx1/AML-1 and CBF beta or CBFbeta. CBF was originally described as a regulator of hematopoiesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that CBF is ...
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UPF2 is a critical regulator of liver development, function and regeneration.
Published: January, 2010

Abstract: BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise fr...
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Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated.
Published: January, 2010

Abstract: BACKGROUND: DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predic...
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Chromatin states of core pluripotency-associated genes in pluripotent, multipotent and differentiated cells.
Published: January, 2010

Abstract: Oct4, Nanog and Sox2 constitute a core of transcription factors controlling pluripotency. Differentiation and reprogramming studies have unraveled a few epigenetic modifications associated in relation to the expression state of OCT4, NANOG and SOX...
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DNA methylation programming and reprogramming in primate embryonic stem cells.
Published: December, 2009

Abstract: DNA methylation is an important epigenetic mechanism, affecting normal development and playing a key role in reprogramming epigenomes during stem cell derivation. Here we report on DNA methylation patterns in native monkey embryonic stem cells (ES...
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An oestrogen-receptor-alpha-bound human chromatin interactome.
Published: November, 2009

Abstract: Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters...
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The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands.
Published: November, 2009

Abstract: Instructive mechanisms are present for induction of DNA methylation, as shown by methylation of specific CpG islands (CGIs) by specific inducers and in specific cancers. However, instructive factors involved are poorly understood, except for invol...
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The histone variant macroH2A is an epigenetic regulator of key developmental genes.
Published: October, 2009

Abstract: The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes is poorly understood. Microarray-based analysis in human male pluri...
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Development of a novel output value for quantitative assessment in methylated DNA immunoprecipitation-CpG island microarray analysis.
Published: October, 2009

Abstract: In DNA methylation microarray analysis, quantitative assessment of intermediate methylation levels in samples with various global methylation levels is still difficult. Here, specifically for methylated DNA immunoprecipitation-CpG island (CGI) mic...
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Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
Published: September, 2009

Abstract: Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune respo...
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Functional connection between deimination and deacetylation of histones.
Published: September, 2009

Abstract: Histone methylation plays key roles in regulating chromatin structure and function. The recent identification of enzymes that antagonize or remove histone methylation offers new opportunities to appreciate histone methylation plasticity in the reg...
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A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos.
Published: September, 2009

Abstract: Epigenetic mechanisms set apart the active and inactive regions in the genome of multicellular organisms to produce distinct cell fates during embryogenesis. Here, we report on the epigenetic and transcriptome genome-wide maps of gastrula-stage Xe...
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High-resolution analysis of epigenetic changes associated with X inactivation.
Published: August, 2009

Abstract: Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes...
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H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.
Published: July, 2009

Abstract: Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification ...
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Histone H3 modifications associated with differentiation and long-term culture of mesenchymal adipose stem cells.
Published: June, 2009

Abstract: Long-term culture of mesenchymal stem cells leads to a loss of differentiation capacity, the molecular mechanism of which remains not understood. We show here that expansion of adipose stem cells (ASCs) to late passage (replicative senescence) is ...
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Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa.
Published: March, 2009

Abstract: Both RNAi-dependent and -independent mechanisms have been implicated in the establishment of heterochromatin domains, which may be stabilized by feedback loops involving chromatin proteins and modifications of histones and DNA. Neurospora crassa s...
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Genome-wide high throughput analysis of DNA methylation in eukaryotes.
Published: March, 2009

Abstract: Cytosine methylation is the quintessential epigenetic mark. Two well-established methods, bisulfite sequencing and methyl-DNA immunoprecipitation (MeDIP) lend themselves to the genome-wide analysis of DNA methylation by high throughput sequencing....
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Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition.
Published: January, 2009

Abstract: Spinal muscular atrophy (SMA), a common neuromuscular disorder, is caused by homozygous absence of the survival motor neuron gene 1 (SMN1), while the disease severity is mainly influenced by the number of SMN2 gene copies. This correlation is not ...
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Tandem ChoRE and CCAAT motifs and associated factors regulate Txnip expression in response to glucose or adenosine-containing molecules.
Published: January, 2009

Abstract: BACKGROUND: Thioredoxin interacting protein (Txnip) is a multifunctional protein involved in regulation of cell cycle events and cellular metabolism. The expression of Txnip is known to be induced by glucose, adenosine-containing molecules, and ot...
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TBP2 is a substitute for TBP in Xenopus oocyte transcription.
Published: January, 2009

Abstract: BACKGROUND: TATA-box-binding protein 2 (TBP2/TRF3) is a vertebrate-specific paralog of TBP that shares with TBP a highly conserved carboxy-terminal domain and the ability to bind the TATA box. TBP2 is highly expressed in oocytes whereas TBP is mor...
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The chromodomain of LIKE HETEROCHROMATIN PROTEIN 1 is essential for H3K27me3 binding and function during Arabidopsis development.
Published: January, 2009

Abstract: Polycomb group (PcG) proteins are essential to maintain gene expression patterns during development. Trans

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