Epigenetics & Chromatin

https://epigeneticsandchromatin.biomedcentral.com

List of Papers (Total 674)

MYC deregulates TET1 and TET2 expression to control global DNA (hydroxy)methylation and gene expression to maintain a neoplastic phenotype in T-ALL

While aberrant DNA methylation is a characteristic feature of tumor cells, our knowledge of how these DNA methylation patterns are established and maintained is limited. DNA methyltransferases and ten-eleven translocation methylcytosine dioxygenases (TETs) function has been found altered in a variety of cancer types. Here, we report that in T cell acute lymphoblastic leukemia (T...

The histone variant H2A.Z in gene regulation

The histone variant H2A.Z is involved in several processes such as transcriptional control, DNA repair, regulation of centromeric heterochromatin and, not surprisingly, is implicated in diseases such as cancer. Here, we review the recent developments on H2A.Z focusing on its role in transcriptional activation and repression. H2A.Z, as a replication-independent histone, has been...

Aberrant methylation-mediated downregulation of lncRNA SSTR5-AS1 promotes progression and metastasis of laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) is among the most common malignant tumors with poor prognosis. Accumulating evidences have identified the important roles of long noncoding RNAs (lncRNAs) in the initiation and progression of various cancer types; however, the global lncRNAs expression profile for metastatic LSCC is limited. In the present study, we screen expression...

Dam mutants provide improved sensitivity and spatial resolution for profiling transcription factor binding

DamID, in which a protein of interest is fused to Dam methylase, enables mapping of protein-DNA binding through readout of adenine methylation in genomic DNA. DamID offers a compelling alternative to chromatin immunoprecipitation sequencing (ChIP-Seq), particularly in cases where cell number or antibody availability is limiting. This comes at a cost, however, of high non-specific...

Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner

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. However, persistent repression has been difficult to achieve in a predictable manner using targeted systems. Here, we report that persistent epigenetic...

The NuA4 acetyltransferase and histone H4 acetylation promote replication recovery after topoisomerase I-poisoning

Histone acetylation plays an important role in DNA replication and repair because replicating chromatin is subject to dynamic changes in its structures. However, its precise mechanism remains elusive. In this report, we describe roles of the NuA4 acetyltransferase and histone H4 acetylation in replication fork protection in the fission yeast Schizosaccharomyces pombe...

The BAF complex in development and disease

The ATP-dependent chromatin remodelling complex BAF (= mammalian SWI/SNF complex) is crucial for the regulation of gene expression and differentiation. In the course of evolution from yeast to mammals, the BAF complex evolved an immense complexity with a high number of subunits encoded by gene families. In this way, tissue-specific BAF function and regulation of development begin...

Combined analysis of dissimilar promoter accessibility and gene expression profiles identifies tissue-specific genes and actively repressed networks

The assay for transposase-accessible chromatin (ATAC-seq) is a powerful method to examine chromatin accessibility. While many studies have reported a positive correlation between gene expression and promoter accessibility, few have investigated the genes that deviate from this trend. In this study, we aimed to understand the relationship between gene expression and promoter...

Coupling of PARP1-mediated chromatin structural changes to transcriptional RNA polymerase II elongation and cotranscriptional splicing

Recently, we showed that PARP1 is involved in cotranscriptional splicing, possibly by bridging chromatin to RNA and recruiting splicing factors. It also can influence alternative splicing decisions through the regulation of RNAPII elongation. In this study, we investigated the effect of PARP1-mediated chromatin changes on RNAPII movement, during transcription and alternative...

Allele-specific RNA-seq expression profiling of imprinted genes in mouse isogenic pluripotent states

Genomic imprinting, resulting in parent-of-origin specific gene expression, plays a critical role in mammalian development. Here, we apply allele-specific RNA-seq on isogenic B6D2F1 mice to assay imprinted genes in tissues from early embryonic tissues between E3.5 and E7.25 and in pluripotent cell lines to evaluate maintenance of imprinted gene expression. For the cell lines, we...

Integrated epigenomic analysis stratifies chromatin remodellers into distinct functional groups

ATP-dependent chromatin remodelling complexes are responsible for establishing and maintaining the positions of nucleosomes. Chromatin remodellers are targeted to chromatin by transcription factors and non-coding RNA to remodel the chromatin into functional states. However, the influence of chromatin remodelling on shaping the functional epigenome is not well understood. Moreover...

Preconception paternal alcohol exposure exerts sex-specific effects on offspring growth and long-term metabolic programming

Although clinical data support an association between paternal alcohol use and deficits in child neurocognitive development, the relationship between paternal drinking and alcohol-induced growth phenotypes remains challenging to define. Using an established mouse model of chronic exposure, previous work by our group has linked preconception paternal alcohol use to sex-specific...

Functional dissection of the developmentally restricted BEN domain chromatin boundary factor Insensitive

Boundaries in the Drosophila bithorax complex delimit autonomous regulatory domains that activate the parasegment (PS)-specific expression of homeotic genes. The Fab-7 boundary separates the iab-6 and iab-7 regulatory domains that control Abd-B expression in PS11 and PS12. This boundary is composed of multiple functionally redundant elements and has two key activities: it blocks...

Integration of DNA methylation patterns and genetic variation in human pediatric tissues help inform EWAS design and interpretation

The widespread use of accessible peripheral tissues for epigenetic analyses has prompted increasing interest in the study of tissue-specific DNA methylation (DNAm) variation in human populations. To date, characterizations of inter-individual DNAm variability and DNAm concordance across tissues have been largely performed in adult tissues and therefore are limited in their...

Distal regulatory elements identified by methylation and hydroxymethylation haplotype blocks from mouse brain

5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that...

Automated in situ chromatin profiling efficiently resolves cell types and gene regulatory programs

Our understanding of eukaryotic gene regulation is limited by the complexity of protein–DNA interactions that comprise the chromatin landscape and by inefficient methods for characterizing these interactions. We recently introduced CUT&RUN, an antibody-targeted nuclease cleavage method that profiles DNA-binding proteins, histones and chromatin-modifying proteins in situ with...

EZH2 variants differentially regulate polycomb repressive complex 2 in histone methylation and cell differentiation

Polycomb repressive complex 2 (PRC2) is responsible for establishing and maintaining histone H3K27 methylation during cell differentiation and proliferation. H3K27 can be mono-, di-, or trimethylated, resulting in differential gene regulation. However, it remains unknown how PRC2 specifies the degree and biological effects of H3K27 methylation within a given cellular context. One...

Physiological effects of KDM5C on neural crest migration and eye formation during vertebrate development

Lysine-specific histone demethylase 5C (KDM5C) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (H3K4 me2/3). KDM5C is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. KDM5C is known to be associated with X-linked mental...

Non-canonical Drosophila X chromosome dosage compensation and repressive topologically associated domains

In animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance in male Drosophila, there is a dosage compensation complex (MSL) that equilibrates X-linked gene expression with the autosomes. There are other potential contributions to dosage compensation. Hemizygous...

DNA replication and repair kinetics of Alu, LINE-1 and satellite III genomic repetitive elements

Preservation of genome integrity by complete, error-free DNA duplication prior to cell division and by correct DNA damage repair is paramount for the development and maintenance of an organism. This holds true not only for protein-encoding genes, but also it applies to repetitive DNA elements, which make up more than half of the human genome. Here, we focused on the replication...

Oxidative stress in sperm affects the epigenetic reprogramming in early embryonic development

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 to repair DNA damage. However, how oxidative DNA lesions in sperm affect early embryonic development remains elusive. Using cattle as model, we...

CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands

The mechanism by which protein complexes interact to regulate the deposition of post-translational modifications of histones remains poorly understood. This is particularly important at regulatory regions, such as CpG islands (CGIs), which are known to recruit Trithorax (TrxG) and Polycomb group proteins. The CxxC zinc finger protein 1 (CFP1, also known as CGBP) is a subunit of...

The methylome of the marbled crayfish links gene body methylation to stable expression of poorly accessible genes

The parthenogenetic marbled crayfish (Procambarus virginalis) is a novel species that has rapidly invaded and colonized various different habitats. Adaptation to different environments appears to be independent of the selection of genetic variants, but epigenetic programming of the marbled crayfish genome remains to be understood. Here, we provide a comprehensive analysis of DNA...

Genome-wide analysis of DNA methylation in buccal cells: a study of monozygotic twins and mQTLs

DNA methylation arrays are widely used in epigenome-wide association studies and methylation quantitative trait locus (mQTL) studies. Here, we performed the first genome-wide analysis of monozygotic (MZ) twin correlations and mQTLs on data obtained with the Illumina MethylationEPIC BeadChip (EPIC array) and compared the performance of the EPIC array to the Illumina...

Control of directionality of chromatin folding for the inter- and intra-domain contacts at the Tfap2c – Bmp7 locus

Contact domains of chromatin serve as a fundamental unit to regulate action of enhancers for target genes. Looping between a pair of CCCTC-binding factor (CTCF)-binding sites in convergent orientations underlies the formation of contact domains, while those in divergent orientations establish domain boundaries. However, every CTCF site is not necessarily engaged in loop or...