Replicational dilution of H3K27me3 in mammalian cells and the role of poised promoters
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ABSTRACT:
PROVIDER: PRJNA528482 | ENA |
REPOSITORIES: ENA
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Project description: Not available
| S-EPMC7376365 | biostudies-literature
Project description:Differential effect of PRC2 loss on gene repression in intestinal stem cells, transit amplifying cells, and differentiated villus cells in intestine is explained by disparity in the rate of cell division and resulting difference in H3K27me3 loss.
2020-01-17 | GSE128671 | GEO
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:In the mouse, germ cells and embryonic stem cells maintain an epigenetically poised (bivalent) state, defined by the simultaneous presence of the opposing histone modifications H3K4me3 and H3K27me3 and by transcriptional repression, at the promoters of many developmental regulatory genes. We compared genome-wide chromatin state in male germ cells of five mammalian and one avian species. We identified a set of 405 genes whose promoters retain poised chromatin in the mammalian germ line throughout mammalian evolution.
2016-05-07 | GSE68507 | GEO
Project description:H3K4me1 distribution at promoters predicts the poised epigenetic state
| PRJNA606462 | ENA
Project description:Genome-wide, little is understood about how proteins organize at inducible promoters before and after in-duction, and to what extent inducible and constitutive architectures depend on cofactors. We report that se-quence-specific transcription factors and their tethered cofactors (e.g., SAGA, Mediator, TUP, NuA4, SWI/SNF, RPD3-L) are already bound to promoters prior to induction (“poised”), rather than recruited upon induction, whereas induction recruits the pre-initiation complex (PIC). Through depletion and/or deletion ex-periments we show that SAGA does not function at constitutive promoters, although a SAGA-independent Gcn5 does acetylate +1 nucleosomes there. At poised promoters, SAGA catalyzes +1 nucleosome acetylation but not PIC assembly. At induced promoters, SAGA catalyzes acetylation, deubiquitylation, and PIC assembly. Surprisingly, SAGA mediates induction by creating a PIC that allows TFIID to stably associate, rather than creating a TFIID-independent PIC, as is generally thought. These findings suggest that inducible systems, where present, evolved on top of constitutive systems.
2022-10-27 | GSE212653 | GEO
Project description:Genome-wide, little is understood about how proteins organize at inducible promoters before and after in-duction, and to what extent inducible and constitutive architectures depend on cofactors. We report that se-quence-specific transcription factors and their tethered cofactors (e.g., SAGA, Mediator, TUP, NuA4, SWI/SNF, RPD3-L) are already bound to promoters prior to induction (“poised”), rather than recruited upon induction, whereas induction recruits the pre-initiation complex (PIC). Through depletion and/or deletion ex-periments we show that SAGA does not function at constitutive promoters, although a SAGA-independent Gcn5 does acetylate +1 nucleosomes there. At poised promoters, SAGA catalyzes +1 nucleosome acetylation but not PIC assembly. At induced promoters, SAGA catalyzes acetylation, deubiquitylation, and PIC assembly. Surprisingly, SAGA mediates induction by creating a PIC that allows TFIID to stably associate, rather than creating a TFIID-independent PIC, as is generally thought. These findings suggest that inducible systems, where present, evolved on top of constitutive systems.
2022-10-27 | GSE212654 | GEO
Project description:Repurposing of promoters and enhancers during mammalian evolution
| PRJNA470431 | ENA
Project description:Expression of histone H3.3K27M mutant proteins in diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and supports the proliferation of DIPG cells in part through silencing of tumor suppressor gene WT1.
2018-07-02 | GSE94834 | GEO
Project description:Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology.
2017-10-26 | GSE89242 | GEO