MicroRNAs maintain bivalency in mouse embryonic stem cells
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ABSTRACT:
PROVIDER: PRJNA257647 | ENA |
REPOSITORIES: ENA
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Project description:The protein Dicer is required for microRNA (miRNA) biogenesis, and therefore Dicer-deficient cells lack all mature, functional miRNAs. Here we investigated the binding of the PRC2 component Ezh2 in wildtype and Dicer-deficient mouse embryonic stem cells genomewide using ChIP-sequencing analysis. Examination of Ezh2 binding in mouse ES cells either proficient (wildtype) or deficient (KO) of the protein Dicer
2016-06-02 | E-GEOD-60160 | biostudies-arrayexpress
Project description:The protein Dicer is required for microRNA (miRNA) biogenesis, and therefore Dicer-deficient cells lack all mature, functional miRNAs. Here we investigated the binding of the PRC2 component Ezh2 in wildtype and Dicer-deficient mouse embryonic stem cells genomewide using ChIP-sequencing analysis.
2016-06-02 | GSE60160 | GEO
Project description: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 transcriptional poising, but the mechanisms that regulate bivalent genes and the bivalent state remain incompletely understood. Examining the contribution of microRNAs (miRNAs) to the regulation of bivalent genes, we found that the miRNA biogenesis enzyme DICER was required for the binding of the PRC2 core components EZH2 and SUZ12, and for the presence of the PRC2-mediated histone modification H3K27me3 at many bivalent genes. Genes that lost bivalency were preferentially upregulated at the mRNA and protein levels. Finally, reconstituting Dicer-deficient ESCs with ESC miRNAs restored bivalent gene repression and PRC2 binding at formerly bivalent genes. Therefore, miRNAs regulate bivalent genes and the bivalent state itself.
| S-EPMC4939759 | biostudies-literature
Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2018-08-02 | MSV000082680 | GNPS
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-06-02 | E-GEOD-60161 | biostudies-arrayexpress
Project description:Epigenetic priming factors establish a permissive epigenetic landscape which is not required until a later developmental or physiological time point, temporally uncoupling the presence of these factors with their phenotypic effects. One classic example of epigenetic priming is in the context of bivalent chromatin, found in pluripotent stem cells and early embryos at key developmental gene promoters marked by both activating-associated H3K4me3 and repressive-associated H3K27me3 histone modifications. It is currently unknown how these bivalent domains are targeted, or precisely how they impact on lineage commitment. Here we show that the small heterodimerising non-enzymatic DNA binding proteins Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) act as epigenetic priming factors to establish bivalency at a subset of developmental genes. Dppa2/4 localise to the +1 nucleosome position of bivalent genes and while they are not required for pluripotency in embryonic stem cells (ESCs), double knockout cells fail to exit pluripotency and to differentiate efficiently, with delays in upregulating bivalently marked lineage genes. Proteomics reveal that Dppa2/4 interact on chromatin with members of the COMPASS and Polycomb complexes important for H3K4me3 and H3K27me3 deposition, respectively. Epigenetic profiling reveals a striking loss of H3K4me3, H3K27me3, and their associated enzymatic machinery at a significant subset of bivalent promoters in Dppa2/4 mutants, in addition to loss of H2A.Z and chromatin accessibility. In wild-type ESCs, these “Dppa2/4-dependent” bivalent promoters are characterised by low H3K4me3 enrichment and breadth, near-absent expression levels and initiating but not elongating RNA polymerase. Notably, Dppa2/4-dependent promoters are less evolutionarily conserved suggesting that they lack additional safeguard measures to maintain bivalency at these genes in the absence of Dppa2/4. Concomitantly with the loss of bivalency, Dppa2/4-dependent bivalent promoters gain DNA methylation and consequently are no longer able to be effectively activated upon ESC differentiation, leading to defects in cell fate acquisition. Our findings reveal a targeting principle for bivalency to developmental gene promoters poising them for future lineage specific gene activation.
2020-05-26 | PXD014981 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-06-02 | GSE60161 | GEO
Project description:In embryonic stem cells (ESCs), bivalency characterizes the chromatin state of developmental gene promoters, simultaneously modified by Mll2 and Polycomb complexes. Despite its essential role in embryogenesis, the function of bivalency is currently unclear. Here we show that Mll2 plays a central role in stem cell genome organization. We generate a catalog of bona-fide bivalent genes in mESCs and demonstrate that loss of Mll2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility and long-range interactions become redistributed, affecting ESC differentiation. We propose that bivalency balances accessibility and long-range connectivity of promoters to modulate developmental gene expression.
2018-09-13 | GSE99530 | GEO
Project description:MicroRNAs maintain bivalency in mouse embryonic stem cells [ChIP-seq]
| PRJNA257650 | ENA
Project description:mouse embryonic fibroblasts, embryonic stem cells, and induced pluripotent stem cells were compared via metabolomic analysis
2013-01-16 | ST000003 | MetabolomicsWorkbench