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58 publications found.

APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients
Published: January, 2018

Abstract: To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name “epi-cblC”. The subjects are compo...
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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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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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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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Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice
Published: March, 2017

Abstract: CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can coope...
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Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots
Published: July, 2016

Abstract: Background In utero and early-life experienced environmental exposures are suggested to play an important role in many multifactorial diseases potentially mediated through lasting effects on the epigenome. As the epigenome in addition remains modi...
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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 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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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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Epigenetic profiling in CD4+ and CD8+ T cells from Graves' disease patients reveals changes in genes associated with T cell receptor signaling
Published: February, 2016

Abstract: In Graves' disease (GD), a combination of genetic, epigenetic and environmental factors causes an autoimmune response to the thyroid gland, characterized by lymphocytic infiltrations and autoantibodies targeting the thyroid stimulating hormone rec...
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DNMT3L enables accumulation and inheritance of epimutations in transgenic Drosophila
Published: January, 2016

Abstract: DNMT3L is an important epigenetic regulator in mammals, integrating DNA methylation and histone modification based epigenetic circuits. Here we show DNMT3L to be a part of the machinery that enables inheritance of epigenetic modifications from one...
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Transcription Factor Repertoire of Homeostatic Eosinophilopoiesis
Published: September, 2015

Abstract: The production of mature eosinophils (Eos) is a tightly orchestrated process with the aim to sustain normal Eos levels in tissues while also maintaining low numbers of these complex and sensitive cells in the blood. To identify regulators of homeo...
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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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An automated method for efficient, accurate and reproducible construction of RNA-seq libraries.
Published: April, 2015

Abstract: BACKGROUND: Integration of RNA-seq expression data with knowledge on chromatin accessibility, histone modifications, DNA methylation, and transcription factor binding has been instrumental for the unveiling of cell-specific local and long-range re...
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Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells
Published: March, 2015

Abstract: DNA methylation is thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells (DCs) with a pathogenic bacteria is associated with rapid chang...
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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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A Novel Role for Kruppel-like Factor 14 (KLF14) in T-Regulatory Cell Differentiation
Published: December, 2014

Abstract: Background & Aims Kruppel-like Factor 14 (KLF14) proteins function as epigenetic reprogramming factors during cell differentiation in many cell populations and in engineered induced pluripotent stem cells. In this study, we determined the func...
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Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation.
Published: October, 2014

Abstract: Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic...
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Automating ChIP-seq Experiments to Generate Epigenetic Profiles on 10,000 HeLa Cells.
Published: October, 2014

Abstract: Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) is a technique of choice for studying protein-DNA interactions. ChIP-seq has been used for mapping protein-DNA interactions and allocating histones modifications. The ...
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Long noncoding RNA modulates alternative splicing regulators in Arabidopsis.
Published: July, 2014

Abstract: Alternative splicing (AS) of pre-mRNA represents a major mechanism underlying increased transcriptome and proteome complexity. Here, we show that the nuclear speckle RNA-binding protein (NSR) and the AS competitor long noncoding RNA (or ASCO-lncRN...
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Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.
Published: July, 2014

Abstract: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with lo...
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Noncoding Transcription by Alternative RNA Polymerases Dynamically Regulates an Auxin-Driven Chromatin Loop.
Published: July, 2014

Abstract: The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidop...
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Two CCAAT box-binding transcription factors redundantly regulate early steps of the legume-rhizobia endosymbiosis.
Published: June, 2014

Abstract: During endosymbiotic interactions between legume plants and nitrogen-fixing rhizobia, successful root infection by bacteria and nodule organogenesis requires the perception and transduction of bacterial lipo-chitooligosaccharidic signal called Nod...
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Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia.
Published: April, 2014

Abstract: BACKGROUND: Aberrant DNA methylation is frequently found in human malignancies including acute myeloid leukemia (AML). While most studies focus on later disease stages, the onset of aberrant DNA methylation events and their dynamics during leukemi...
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Stable methylation at promoters distinguishes Epiblast Stem Cells from Embryonic Stem Cells and the in vivo epiblast.
Published: April, 2014

Abstract: Embryonic Stem Cells (ESCs) and Epiblast Stem Cells (EpiSCs) are the in vitro representatives of naïve and primed pluripotency, respectively. It is currently unclear how their epigenomes underpin the phenotypic and molecular characteristics o...
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MBD4 cooperates with DNMT1 to mediate methyl-DNA repression and protects mammalian cells from oxidative stress.
Published: April, 2014

Abstract: Oxidative stress induces genome-wide remodeling of the chromatin structure. In this study, we identify Methyl-CpG Binding Protein 4 (MBD4), a multifunctional enzyme involved in DNA demethylation, base excision repair, and gene expression regulatio...
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Human-specific epigenetic variation in the immunological Leukotriene B4 Receptor (LTB4R/BLT1) implicated in common inflammatory diseases.
Published: March, 2014

Abstract: BACKGROUND: Common human diseases are caused by the complex interplay of genetic susceptibility as well as environmental factors. Due to the environment's influence on the epigenome, and therefore genome function, as well as conversely the genome'...
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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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Differential methylation of the TRPA1 promoter in pain sensitivity.
Published: January, 2014

Abstract: Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further ...
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Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3.
Published: January, 2014

Abstract: DNA demethylation has been primarily studied in the context of development biology, cell fate, and cancer, with less attention on inflammation. In this article, we investigate the association between DNA methylation and production of the chemoattr...
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Toxoplasma gondii inhibits IFN-γ- and IFN-β-induced host cell STAT1 transcriptional activity by increasing the association of STAT1 with DNA.
Published: November, 2013

Abstract: The IFN-γ response, mediated by the STAT1 transcription factor, is crucial for host defense against the intracellular pathogen Toxoplasma gondii, but prior infection with Toxoplasma can inhibit this response. Recently it was reported that th...
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Reactive Oxygen Species Induce Epigenetic Instability through the Formation of 8-Hydroxydeoxyguanosine in Human Hepatocarcinogenesis.
Published: November, 2013

Abstract: Chronic hepatitis C (CHC) triggers oxidative stress and contributes to the emergence of hepatocellular carcinoma (HCC). We previously reported that tumor suppressor gene (TSG) methylation is a critical factor during the early stages of hepatocarci...
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Lack of decorin expression by human bladder cancer cells offers new tools in the therapy of urothelial malignancies.
Published: October, 2013

Abstract: Decorin, a multifunctional small leucine-rich extracellular matrix proteoglycan, has been shown to possess potent antitumour activity. However, there is some uncertainty whether different cancer cells express decorin in addition to non-malignant s...
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DNA methylation analysis of murine hematopoietic side population cells during aging.
Published: October, 2013

Abstract: Stem cells have been found in most tissues/organs. These somatic stem cells produce replacements for lost and damaged cells, and it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible ...
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Global alterations of DNA methylation in cholangiocarcinoma targets the Wnt signaling pathway
Published: September, 2013

Abstract: The molecular mechanisms underlying the genesis of cholangiocarcinomas (CCs) are poorly understood. Epigenetic changes such as aberrant hypermethylation and subsequent atypical gene expression are characteristic features of most human cancers. In ...
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Integrated virus-host methylome analysis in head and neck squamous cell carcinoma
Published: September, 2013

Abstract: One in six cancers worldwide is caused by infection and human papillomavirus (HPV) is one of the main culprits. To better understand the dynamics of HPV integration and its effect on both the viral and host methylomes, we conducted whole-genome DN...
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Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for TET2.
Published: July, 2013

Abstract: Isocitrate dehydrogenase (IDH) genes 1 and 2 are frequently mutated in acute myeloid leukaemia (AML), low-grade glioma, cholangiocarcinoma (CC) and chondrosarcoma (CS). For AML, low-grade glioma and CC, mutant IDH status is associated with a DNA h...
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HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas.
Published: June, 2013

Abstract: High-risk types of human papilloma virus (HPV) are increasingly associated with oropharyngeal squamous cell carcinoma (OPSCC). Strikingly, patients with HPV-positive OPSCC are highly curable with ionizing radiation and have better survival compare...
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SOX2 co-occupies distal enhancer elements with distinct POU factors in ESCs and NPCs to specify cell state.
Published: February, 2013

Abstract: SOX2 is a master regulator of both pluripotent embryonic stem cells (ESCs) and multipotent neural progenitor cells (NPCs); however, we currently lack a detailed understanding of how SOX2 controls these distinct stem cell populations. Here we show ...
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Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.
Published: February, 2013

Abstract: BACKGROUND: Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic mod...
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Linking proteomic and transcriptional data through the interactome and epigenome reveals a map of oncogene-induced signaling.
Published: February, 2013

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

Abstract: AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understa...
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Nano-MeDIP-seq: Methylome analysis using low DNA concentrations (Prot 58)
Published: December, 2012

Abstract: To understand the functional consequences of DNA methylation on phenotypic plasticity, a genome - wide analysis should be embraced. This in turn requires a technique that balances accuracy, genome coverage, resolution and cost, yet is low in DNA i...
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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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HMGA1 Reprograms Somatic Cells into Pluripotent Stem Cells by Inducing Stem Cell Transcriptional Networks.
Published: November, 2012

Abstract: BACKGROUND: Although recent studies have identified genes expressed in human embryonic stem cells (hESCs) that induce pluripotency, the molecular underpinnings of normal stem cell function remain poorly understood. The high mobility group A1 (HMGA...
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Human-specific CpG "beacons" identify loci associated with human-specific traits and disease.
Published: October, 2012

Abstract: Regulatory change has long been hypothesized to drive the delineation of the human phenotype from other closely related primates. Here we provide evidence that CpG dinucleotides play a special role in this process. CpGs enable epigenome variabilit...
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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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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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Methylome analysis using MeDIP-seq with low DNA concentrations.
Published: March, 2012

Abstract: DNA methylation is an epigenetic mark that has a crucial role in many biological processes. To understand the functional consequences of DNA methylation on phenotypic plasticity, a genome-wide analysis should be embraced. This in turn requires a t...
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Quality control and single nucleotide resolution analysis of methylated DNA immunoprecipitation products.
Published: December, 2010

Abstract: DNA methylation patterns are altered in many diseases, and their analysis has become of great interest. Methylated DNA immunoprecipitation (MeDIP) is a simple method to enrich the methylated fraction of the genome. However, it has been difficult t...
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Whole-genome DNA methylation profiling using MethylCap-seq.
Published: November, 2010

Abstract: MethylCap-seq is a robust procedure for genome-wide profiling of DNA methylation. The approach consists of the capture of methylated DNA using the MBD domain of MeCP2, and subsequent next-generation sequencing of eluted DNA. Elution of the capture...
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Quantitative comparison of genome-wide DNA methylation mapping technologies.
Published: October, 2010

Abstract: DNA methylation plays a key role in regulating eukaryotic gene expression. Although mitotically heritable and stable over time, patterns of DNA methylation frequently change in response to cell differentiation, disease and environmental influences...
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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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Using ChIP-Seq Technology to Generate High-Resolution Profiles of Histone Modifications

Abstract: The dynamic modification of DNA and histones plays a key role in transcriptional regulation through - altering the packaging of DNA and modifying the nucleosome surface. These chromatin states, also referred to as the epigenome, are distinctive fo...
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AutoMeDIP-seq: A high-throughput, whole genome, DNA methylation assay

Abstract: DNA methylation is an epigenetic mark linking DNA sequence and transcription regulation, and therefore plays an important role in phenotypic plasticity. The ideal whole genome methylation (methylome) assay should be accurate, affordable, high-thro...
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Genome-Wide Analysis of Methylation in Bovine Clones by Methylated DNA Immunoprecipitation (MeDIP)

Abstract: Methylated DNA immunoprecipitation (MeDIP), when coupled to high-throughput sequencing or microarray hybridization, allows for the identification of methylated loci at a genome-wide scale. Genomic regions affected by incomplete reprogramming after...
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Enrichment of Methylated DNA by Methyl-CpG Immunoprecipitation.

Abstract: Normal DNA methylation is an epigenetic modification required for proper development. Aberrant DNA methylation, in contrast, is frequently observed in many different malignancies including leukemias and lymphomas. Global DNA methylation profiling ...
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