Chip-chip in the complete absence of DNA methylation with H3K4me2, H3K9me2 and H3K27me3
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE36670 | GEO | 2021/02/17
REPOSITORIES: GEO
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Project description:Using all three CpG DNA methyltransferases, Dnmt1, Dnmt3a and Dnmt3b deficient (TKO) mouse ES cells and TKO ntTS cells, we examined three histone modifications H3K4me2, H3K27me3 and H3K9me2, of promoter region in ES, TS and Flk1+ mesodermal cells with WT or TKO background by ChIP-chip analysis. Global profile analysis of gene expression and histone modification showed that the difference of profiles was mainly lineage dependent. Although the effects of DNA methylation loss in three lineages were modest, H3K27me3 is most sensitive to DNA methylation among three modifications. Interestingly, differentially expressed genes between WT and TKO cells were also lineage dependent and small number of genes was overlapped between lineages. Our further analysis showed that the profiles of H3K27me3 modifications were dynamically changed between lineages, especially in TS cells, and the pattern of H3K27me3 modification was defectively established by loss of DNA methylation. Our data suggest that DNA methylation contributes to lineage dependent expression regulation by collaborating with histone modification.
2021-02-17 | GSE36663 | GEO
Project description:Using all three CpG DNA methyltransferases, Dnmt1, Dnmt3a and Dnmt3b deficient (TKO) mouse ES cells and TKO ntTS cells, we examined three histone modifications H3K4me2, H3K27me3 and H3K9me2, of promoter region in ES, TS and Flk1+ mesodermal cells with WT or TKO background by ChIP-chip analysis. Global profile analysis of gene expression and histone modification showed that the difference of profiles was mainly lineage dependent. Although the effects of DNA methylation loss in three lineages were modest, H3K27me3 is most sensitive to DNA methylation among three modifications. Interestingly, differentially expressed genes between WT and TKO cells were also lineage dependent and small number of genes was overlapped between lineages. Our further analysis showed that the profiles of H3K27me3 modifications were dynamically changed between lineages, especially in TS cells, and the pattern of H3K27me3 modification was defectively established by loss of DNA methylation. Our data suggest that DNA methylation contributes to lineage dependent expression regulation by collaborating with histone modification.
2021-02-17 | GSE36662 | GEO
Project description:In this study, we mapped modification of lysine 4 and lysine 27 of histone H3 genome-wide in a series of mouse embryonic stem cells (mESCs) varying in DNA methylation levels based on knock-out and reconstitution of DNA methyltransferases (DNMTs). We extend previous studies showing cross-talk between DNA methylation and histone modifications by examining a breadth of histone modifications, causal relationships, and direct effects. Our data shows a causal regulation of H3K27me3 at gene promoters as well as H3K27ac and H3K27me3 at tissue-specific enhancers. We also identify isoform differences between DNMT family members. This study provides a comprehensive resource for the study of the complex interplay between DNA methylation and histone modification landscape. Histone ChIP-seq of H3K4me3, H3K27me3, H3K4me1, and H3K27ac were performed on wild-type, Dnmt triple knock-out (Dnmt1/3a/3b; TKO), Dnmt double knock-out (Dnmt3a/3b; DKO), and respective reconstitution mouse embryonic stem cell lines
2016-08-02 | E-GEOD-77002 | biostudies-arrayexpress
Project description:In this study, we mapped modification of lysine 4 and lysine 27 of histone H3 genome-wide in a series of mouse embryonic stem cells (mESCs) varying in DNA methylation levels based on knock-out and reconstitution of DNA methyltransferases (DNMTs). We extend previous studies showing cross-talk between DNA methylation and histone modifications by examining a breadth of histone modifications, causal relationships, and direct effects. Our data shows a causal regulation of H3K27me3 at gene promoters as well as H3K27ac and H3K27me3 at tissue-specific enhancers. We also identify isoform differences between DNMT family members. This study provides a comprehensive resource for the study of the complex interplay between DNA methylation and histone modification landscape. RNA-seq performed on wild-type, Dnmt triple knock-out (Dnmt1/3a/3b; TKO), Dnmt double knock-out (Dnmt3a/3b; DKO), and respective reconstitution mouse embryonic stem cell lines
2016-08-02 | E-GEOD-77003 | biostudies-arrayexpress
Project description:In this study, we mapped modification of lysine 4 and lysine 27 of histone H3 genome-wide in a series of mouse embryonic stem cells (mESCs) varying in DNA methylation levels based on knock-out and reconstitution of DNA methyltransferases (DNMTs). We extend previous studies showing cross-talk between DNA methylation and histone modifications by examining a breadth of histone modifications, causal relationships, and direct effects. Our data shows a causal regulation of H3K27me3 at gene promoters as well as H3K27ac and H3K27me3 at tissue-specific enhancers. We also identify isoform differences between DNMT family members. This study provides a comprehensive resource for the study of the complex interplay between DNA methylation and histone modification landscape. Reduced representation bisulfite sequencing (RRBS) performed on wild-type, Dnmt triple knock-out (Dnmt1/3a/3b; TKO), Dnmt double knock-out (Dnmt3a/3b; DKO), and respective reconstitution mouse embryonic stem cell lines.
2016-08-02 | E-GEOD-84103 | biostudies-arrayexpress
Project description:Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation, an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, which presents a major roadblock for dissecting the precise roles of PRC2 activity during lineage commitment. While recent studies suggest that loss of H3K27me3 leads to changes in DNA methylation in ESCs, how these two pathways coordinate to regulate gene expression programs during lineage commitment is poorly understood. Here, we analyzed gene expression and DNA methylation levels in several PRC2 mutant ESC lines that maintain varying levels of H3K27me3. We found that maintenance of intermediate levels of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). However, genes that function to specify other lineages failed to be repressed, suggesting that PRC2 activity is necessary for lineage fidelity. We also found that H3K27me3 is antagonistic to DNA methylation in cis. Furthermore, loss of H3K27me3 leads to a gain in promoter DNA methylation in developmental genes in ESCs and in lineage genes during differentiation. Thus, our data suggest a role for PRC2 in coordinating dynamic gene repression while protecting against inappropriate promoter DNA methylation during differentiation. Embryonic Stem Cell (ESC) lines mutant for PRC2 core components Suz12 (Suz12GT and Suz12delta) and Eed (Eednull) were subjected to in vitro directed differentiation down the spinal motor neuron lineage. ESCs and day 5 differentiated cells from the three mutant lines and wild-type were used for H3K27me3 ChIP-seq.
2014-11-17 | E-GEOD-53505 | biostudies-arrayexpress
Project description:Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation, an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, which presents a major roadblock for dissecting the precise roles of PRC2 activity during lineage commitment. While recent studies suggest that loss of H3K27me3 leads to changes in DNA methylation in ESCs, how these two pathways coordinate to regulate gene expression programs during lineage commitment is poorly understood. Here, we analyzed gene expression and DNA methylation levels in several PRC2 mutant ESC lines that maintain varying levels of H3K27me3. We found that maintenance of intermediate levels of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). However, genes that function to specify other lineages failed to be repressed, suggesting that PRC2 activity is necessary for lineage fidelity. We also found that H3K27me3 is antagonistic to DNA methylation in cis. Furthermore, loss of H3K27me3 leads to a gain in promoter DNA methylation in developmental genes in ESCs and in lineage genes during differentiation. Thus, our data suggest a role for PRC2 in coordinating dynamic gene repression while protecting against inappropriate promoter DNA methylation during differentiation. Embryonic Stem Cell (ESC) lines mutant for PRC2 core components Suz12 (Suz12GT and Suz12delta) and Eed (Eednull) were subjected to in vitro directed differentiation down the spinal motor neuron lineage. ESCs and day 5 differentiated cells from the three mutant lines and wild-type were used for Reduced Representation Bisulfite Sequencing (RRBS).
2014-11-17 | E-GEOD-53507 | biostudies-arrayexpress
Project description:Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation, an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, which presents a major roadblock for dissecting the precise roles of PRC2 activity during lineage commitment. While recent studies suggest that loss of H3K27me3 leads to changes in DNA methylation in ESCs, how these two pathways coordinate to regulate gene expression programs during lineage commitment is poorly understood. Here, we analyzed gene expression and DNA methylation levels in several PRC2 mutant ESC lines that maintain varying levels of H3K27me3. We found that maintenance of intermediate levels of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). However, genes that function to specify other lineages failed to be repressed, suggesting that PRC2 activity is necessary for lineage fidelity. We also found that H3K27me3 is antagonistic to DNA methylation in cis. Furthermore, loss of H3K27me3 leads to a gain in promoter DNA methylation in developmental genes in ESCs and in lineage genes during differentiation. Thus, our data suggest a role for PRC2 in coordinating dynamic gene repression while protecting against inappropriate promoter DNA methylation during differentiation. Embryonic Stem Cell (ESC) lines mutant for PRC2 core components Suz12 (Suz12GT and Suz12delta) and Eed (Eednull) were subjected to in vitro directed differentiation down the spinal motor neuron lineage. ESCs and day 5 differentiated cells from the three mutant lines and wild-type were used for RNA-seq.
2014-11-17 | E-GEOD-53506 | biostudies-arrayexpress
Project description: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-sequencing (ChIP- BS-seq) as an approach to quantitatively assess DNA methylation patterns associated with chromatin modifications or chromatin-associated factors directly. A chromatin- immunoprecipitation (ChIP)-capturing step is used to obtain a restricted representation of the genome occupied by the epigenetic feature of interest, for which a single-base resolution DNA methylation map is then generated. When applied to H3 lysine 27 tri- methylation (H3K27me3), we found that H3K27me3 and DNA methylation are compatible throughout most of the genome, except for CpG islands, where these two marks are mutually exclusive. Further ChIP-BS-seq-based analysis in Dnmt triple- knock-out (TKO) embryonic stem cells revealed that total loss of CpG methylation is associated with alteration of H3K27me3 levels throughout the genome: H3K27me3 in localized peaks is decreased while broad local enrichments (BLOCs) of H3K27me3 are formed. At an even broader scale, these BLOCs correspond to regions of high DNA methylation in wild-type ES cells, suggesting that DNA methylation prevents H3K27me3 deposition locally and at megabase scale. Our strategy provides an unique way of investigating global interdependencies between DNA methylation and other chromatin features. ChIP (chromatin immunoprecipitation) is followed by bisulfite conversion and deep sequencing to directly assess DNA methylation levels in captured chromatin fragments (ChIP-BS-seq). We used ChIP-BS-seq to study the potential global cross-talk between H3K27me3 and DNA methylation, which are both linked to repression. First, we used capturing of methylated DNA, followed by bisulfite-deep sequencing (MethylCap-BS-seq). Genomic DNA isolated from normal and tumor colon tissues was used for MethylCap-BS-seq as well as for conventional MethylCap-seq experiments. Second, we performed ChIP-BS-seq on H3K27me3, using HCT116 colon carcinoma cells. Third, to further study the relevance of the observations, we generated genome-wide profiles for H3K27me3 and DNA methylation by conventional ChIP-seq and MethylCap-seq, and RNA-seq, respectively. Finally, we performed H3K27me3-ChIP-BS-seq and MethylCap-seq on wild-type mouse ES cells as well as Dnmt-triple-knockout (TKO) mouse ES cells.
2012-03-27 | E-GEOD-28254 | biostudies-arrayexpress
Project description:The ground state of pluripotency is defined as a basal proliferative state free of epigenetic restriction, represented by mouse embryonic stem cells (ESCs) cultured with two kinase inhibitors (so-called “2i”). Through comparison with serum-grown ESCs, we identify epigenetic features characterizing 2i ESCs by proteome profiling of chromatin including post-translational histone modifications. The most prominent difference is H3K27me3 and its enzymatic writer complex PRC2 that are highly abundant on eu- and heterochromatin in 2i ESCs, with H3K27me3 redistributing outside canonical PRC2 targets in a CpG-dependent fashion. Using PRC2-deficient 2i ESCs, we identify epigenetic crosstalk with H3K27me3, including significant increases in H4 acetylation and DNA methylation. This suggests that the unique H3K27me3 configuration protects 2i ESCs from preparation to lineage priming. Interestingly, removal of DNA methylation in PRC2-deficient 2i ESCs lacking H3K27me3 using 5-azacytidine hardly affected ESC viability and transcriptome, showing that ESCs are independent of both major repressive epigenetic marks.
2018-11-21 | PXD007154 | Pride