Ontology highlight
ABSTRACT:
PROVIDER: PRJNA130081 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE23907: Histone H3K27ac separates active from poised enhancers and predicts developmental state (gene expression data) GSE24164: ChIP-Seq of chromatin marks at distal enhancers in Mouse Embryonic Stem Cells and adult tissues. Refer to individual Series
2010-10-31 | E-GEOD-24165 | biostudies-arrayexpress
Project description:Histone H3K27ac separates active from poised enhancers and predicts developmental state (gene expression data)
| PRJNA133189 | ENA
Project description:Developmental programs are controlled by transcription factors and chromatin regulators, which maintain specific gene expression programs through epigenetic modification of the genome. These regulatory events at enhancers contribute to the specific gene expression programs that determine cell state and the potential for differentiation into new cell types. While enhancer elements are known to be associated with certain histone modifications, and transcription factors, the relationship of these modifications to gene expression and developmental state has not been clearly defined. Here we interrogate the epigenetic landscape of enhancer elements in embryonic stem cells and several adult tissues in the mouse. We find that histone H3K27ac distinguishes active enhancers from inactive/poised enhancer elements, thus providing clues to current cell state and further developmental potential. Gene expression profiling was performed in mouse ES, NPC, liver, and pro-B
2010-10-31 | E-GEOD-23907 | biostudies-arrayexpress
Project description:Cell fate transitions involve integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of the genomic sequences that control the earliest steps of human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs) unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, and monomethylation of histone H3 at lysine 4 (H3K4me1). In addition, the elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized enhancers active in hESCs, and are generally located proximally to genes expressed in hESCs and in the epiblast. In contrast, the elements within the second class, which we termed M-bM-^@M-^\poised enhancersM-bM-^@M-^], are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3) and are linked to genes inactive in hESCs and involved in orchestrating early steps in mammalian development, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of these elements acquires a chromatin signature associated with active enhancers. Remarkably, when assayed in zebrafish embryos, human poised enhancer elements are able to direct cell type and stage specific expression patterns characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that enhancers are epigenetically pre-marked and suggest a heretofore unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the unique chromatin signature associated with poised enhancers allowed us to uncover over 2,000 putative developmental regulatory sequences, thereby creating an invaluable resource for future studies and isolation of transient, rare cell populations representing early steps of human development. For GSM602289-90: RNA-seq experiments in human ESC and neuroectodermal (NEC) speheres For GSM602291-303: Genome-wide analysis of p300, H3K4me3, H3K4me1, H3K27me3 and H3K27ac in human embryonic stem cells (ESC) and neuroectoderm cells (NEC). Additionally, in H9 ESC ChIP-seq were alsoe obtained for BRG1 and FAIRE-seq was also performed.
2010-12-15 | E-GEOD-24447 | biostudies-arrayexpress
Project description:The regulatory elements that direct tissue-specific gene expression in the developing mammalian embryo remain largely unknown. Although chromatin profiling has proven to be a powerful method for mapping regulatory sequences in cultured cells, chromatin states characteristic of active developmental enhancers have not been directly identified in embryonic tissues. Here we use whole transcriptome analysis coupled with genome-wide profiling of H3K27ac and H3K27me3 to map chromatin states and enhancers in mouse embryonic forelimb and hindlimb. We show that gene expression differences between forelimb and hindlimb, and between limb and other embryonic cell types, are correlated with tissue-specific H3K27ac signatures at promoters and distal sites. Using H3K27ac profiles, we identified 28,377 putative enhancers, many of which are likely to be limb-specific based on strong enrichment near genes highly expressed in the limb and comparisons with tissue-specific p300 sites and known enhancers. We describe a chromatin state signature associated with active developmental enhancers, defined by high levels of H3K27ac marking, nucleosome displacement, hypersensitivity to sonication, and strong depletion of H3K27me3. We also find that developmental enhancers exhibit components of this signature, including hypersensitivity, H3K27ac enrichment and H3K27me3 depletion, at lower levels in tissues in which they are not active. Our results establish histone modification profiling as a tool for developmental enhancer discovery, and suggest that enhancers maintain an open chromatin state in multiple embryonic tissues independent of their activity level. Examination of genome wide H3K27ac and H3K27me3 histone modifications and gene expression in early mouse embryonic limb tissue.
2012-03-16 | E-GEOD-30641 | biostudies-arrayexpress
Project description:Characterisation of different histone modifications is crucial to understand gene regulation. In order to study the most predictive histone modification for active enhancers we created unbiased set of enhancers and used machine learning approach. Our approach revealed an unconventional histone modification H2BK20ac as most efficient marker of active enhancers. H2BK20ac also showed superior coverage of tissue specific active enhancers in complex invivo samples. Adding H2BK20ac to set of conventional histone modifications lead to identification of new chromatin state which could be active enhancers. H2BK20ac tends to occur only at cell-type specific active promoters and showed higher specificity for related disease mutations than H3K27ac and other histone modifications. Using transient state of BV2 microglia cells after lipopolysaccharide based activation, we found that H2BK20ac also marks cell-state specific cis-regulatory elements. Further analysis using inhibition of TGF-beta pathway in BV2 cells and LPS stimulation, revealed differential patterns of H2BK20ac and H3K27ac at genome locations associated with opposite roles response to stmulation. Our study about H2BK20ac hints about a new mechanism of regulation of cell-type specificity and a distinct mode of action of pathways to maintain balance between cell-responses. Chip-seq of H2BK20ac and other histone modifcation was performed in 3 cell types and embryonic mouse forebrain. The sensitivity for active enhancers was compared for different histone modification ChIP-seq.The level of H2BK20ac at promoters and enhancers was assesed for relationship to cell-type specific expression. H2BK20ac signals were also analysed during cell-state transition when microgila are stimulated by LPS
2016-02-25 | E-GEOD-72886 | biostudies-arrayexpress
Project description:The discovery of TET proteins, enzymes that oxidize 5-methylcytosine (5mC) in DNA, has revealed novel mechanisms for the regulation of DNA methylation. We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T cell development in the thymus and T cell differentiation in the periphery. We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages, and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers, and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect. Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T cell development and differentiation. Examine the distribution of the H3K27Ac in DP T cells. The presence of H3K27Ac in enhancers enable us to distinguish poised(H3Kme1 enriched, but devoid of H3K27Ac) versus active enhancers (enriched for H3K4me1 and H3K27Ac).
2014-08-04 | E-GEOD-59117 | biostudies-arrayexpress
Project description:Post-translational modifications on histone tails are closely correlated to transcriptional states. One such modification is monomethylation on lysine 4 of histone 3(H3K4me1), a mark that has been linked to enhancers. Identifying regions enriched for H3K4me1 and depleted in H3K4me3, or regions enriched for both H3K4me1 and H3K27ac, has proven to be a feasible enhancer discovery method. At the same time, not all H3K4me1-enriched regions correspond to enhancers. H3K4me1 marks also exist at promoters, which implies that the H3K4me1 modification may have a context-dependent role in regulating transcription. We report distinct patterns of H3K4me1 that predict transcriptional regulatory states at promoters in germ cells and ESCs. We examined ChIP-seq data for H3K4me1, H3K4me3, H3K27me3, and H3K27ac in mouse and human male germ cells, and found that H3K4me1 peak density around the transcription start sites (TSS) exhibits either a broad bimodal profile or a narrower unimodal profile centered at the TSS. We then examined the position of the H3K4me1 marks relative to H3K4me3, and found that unimodal H3K4me1 directly at the TSS predicts a poised (H3K4me1/H3K27me3 bivalent) state of chromatin, while bimodal H3K4me1 flanking the TSS predicts an active state. We conclude that unimodal H3K4me1 centered on the TSS is a characteristic feature of the poised epigenetic state in ESCs and germ cells. Note: H3K4me1 and H3K27ac data are included in this GEO accession; H3K4me3 and H3K27me3 were released in GSE68507.
2020-04-05 | GSE145225 | GEO
Project description:We applied ChIP-Seq on two histone marks: H3K4me1 and H3K27ac in healthy human neutrophils. After peak calling, we obtained the peak regions enriched with H3K4me1 and H3K27ac histone marks and identifed aciive enhancers (H3K27ac+/H3K4me1+) and H3K27ac active enhancers (H3K27ac+/H3K4me1-) in human neutrophils and checked whether those enhancers are located in the LD blocks of 22 SNPs associtated with Juvenile Idiopathic Arthritis. Identification of active enhancers in human neutrohils
2015-06-12 | E-GEOD-66896 | biostudies-arrayexpress
Project description:We describe the use of a novel DNA modification-dependent restriction endonuclease AbaSI coupled with sequencing (Aba-seq) to map high-resolution hydroxymethylome of mouse E14 embryonic stem cells. The specificity of AbaSI enables sensitive detection of 5hmC at low occupancy regions. Bioinformatic analysis suggests 5hmCs in genic regions closely follows the 5mC distribution. 5hmC is generally depleted in CpG islands and only enriched in a small set of repetitive elements. A regularly spaced and oscillating 5hmC pattern was observed at the binding sites of CTCF. 5hmC is enriched at the poised enhancers with the mono-methylated histone H3 lysine 4 (H3K4me1) marks, but not at the active enhancers with the acetylated histone H3 lysine 27 (H3K27Ac) marks. Non-CG hydroxymethylation appears to be prevalent in the mitochondrial genome. We propose that some amounts of transiently stable 5hmCs may indicate a poised epigenetic state or de-methylation intermediate, while others may suggest a locally accessible chromosomal environment to the TET enzymatic apparatus. Mapping of genomic 5-hydroxymethylcytosine in mouse embryonic stem cell by enzymatic digistion of AbaSI coupled with high-throughput sequencing, in replicates.
2013-01-01 | E-GEOD-42898 | biostudies-arrayexpress