Exploration of PRC2 sigal at gene promoters
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67624 | GEO | 2015/05/01
SECONDARY ACCESSION(S): PRJNA280510
REPOSITORIES: GEO
Similar Datasets
Project description:Performed H3K27me3 ChIP-chip analysis to defien genomic regions with this mark, which indicates the presence of the PRC2 complex Untreated SW-13 adrenocortical carcinoma cells were lysed and ChIP analysis was performed to pull down H3K27me3 labelled chromatin. Purified DNA of that chromatin was hybridized to Agilent ChIP arrays. This experiment was repeated 3 times.
2015-05-01 | E-GEOD-67624 | biostudies-arrayexpress
Project description:The core Polycomb Repressor Complex 2 (PRC2) is composed of Ezh1/2, Suz12, Eed and is responsible for mediating both H3K27me2 and H3K27me3. However, the mechanisms by which PRC2 demarcates these two repressive modifications in the genome are unknown. In a functional screen, we identified the H3K36 dimethyltransferase Nsd1 as a modulator of PRC2-mediated di- and trimethylation of H3K27. ChIP-Seq analysis following the depletion of Nsd1 revealed a global reduction in H3K36me2 and an increase in H3K27me3 at sites previously marked by H3K27me2. We show that the H3K36me2 at H3K27me2 marks co-occupy regions and provide evidence that the presence of H3K36me2 functions to restrict the spatial distribution of Polycomb mediated H3K27me3 domains.
2018-03-29 | GSE107773 | GEO
Project description:The core Polycomb Repressor Complex 2 (PRC2) is composed of Ezh1/2, Suz12, Eed and is responsible for mediating both H3K27me2 and H3K27me3. However, the mechanisms by which PRC2 demarcates these two repressive modifications in the genome are unknown. In a functional screen, we identified the H3K36 dimethyltransferase Nsd1 as a modulator of PRC2-mediated di- and trimethylation of H3K27. ChIP-Seq analysis following the depletion of Nsd1 revealed a global reduction in H3K36me2 and an increase in H3K27me3 at sites previously marked by H3K27me2. We show that the H3K36me2 at H3K27me2 marks co-occupy regions and provide evidence that the presence of H3K36me2 functions to restrict the spatial distribution of Polycomb mediated H3K27me3 domains.
2018-09-15 | GSE86925 | GEO
Project description:Broad chromatin marks are often spread through read-write loops, where chromatin modifiers bind to their products. Polycomb domains are broad repressive chromatin regions in metazoan species, defined by the repressive chromatin mark H3 lysine 27 tri-methyl (H3K27me3) of the Polycomb repressive complex 2 (PRC2). PRC2 is an allosteric enzyme: it switches into a stimulated state by its own H3K27me3 product in a positive feedback loop that maintains Polycomb domains. Yet, it is unknown what prevents this PRC2-H3K27me3 positive feedback loop from spreading H3K27me3 indefinitely. Here we show that mutant mouse embryos, defective in the allosteric activation of PRC2 by its accessory subunits, exhibit a homeotic transformation characteristic of a Polycomb gain-of-function. The same mutations in mouse embryonic stem cells lead to a global gain of H3K27me3 and its spread beyond Polycomb domains. Collectively, we show that the allosteric effector activity of PRC2 accessory subunits restricts H3K27me3 deposition and prevents its spread beyond Polycomb domains.
2026-01-27 | GSE278724 | GEO
Project description:Polycomb Repressive Complex 2 (PRC2) plays an essential role in development by catalysing trimethylation of histone H3 lysine 27 (H3K27me3), resulting in gene repression. PRC2 consists of two sub-complexes, PRC2.1 and PRC2.2, in which the PRC2 core associates with distinct ancillary subunits such as MTF2 and JARID2, respectively. Both MTF2, present in PRC2.1, and JARID2, present in PRC2.2, play a role in core PRC2 recruitment to target genes in mouse embryonic stem cells (mESCs). However, it remains unclear how these distinct sub-complexes cooperate to establish H3K27me3 domains. Here, we combine a range of Polycomb mutant mESCs with chemical inhibition of PRC2 catalytic activity, to systematically dissect their relative contributions to PRC2 binding to target loci. We find that PRC2.1 and PRC2.2 mediate two distinct paths for recruitment, with mutually reinforced binding. Part of the cross-talk between PRC2.1 and PRC2.2 occurs via their catalytic product H3K27me3, which is bound by the PRC2 core-subunit EED, thereby mediating a positive feedback. Strikingly, removal of either JARID2 or H3K27me3 only has a minor effect on PRC2 recruitment, whereas their combined ablation largely attenuates PRC2 recruitment. This strongly suggests an unexpected redundancy between JARID2 and EED-H3K27me3-mediated recruitment of PRC2. Furthermore, we demonstrate that all core PRC2 recruitment occurs through the combined action of MTF2-mediated recruitment of PRC2.1 to DNA and PRC1-mediated recruitment of JARID2-containing PRC2.2. Both axes of binding are supported by EED-H3K27me3 positive feedback, but to a different degree. Finally, we provide evidence that PRC1 and PRC2 mutually reinforce reciprocal binding. Together, these data disentangle the interdependent and cooperative interactions between Polycomb complexes that are important to establish Polycomb repression at target sites.
2020-08-07 | PXD014290 | Pride
Project description:Polycomb Repressive Complex 2 (PRC2) plays an essential role in development by catalysing trimethylation of histone H3 lysine 27 (H3K27me3), resulting in gene repression. PRC2 consists of two sub-complexes, PRC2.1 and PRC2.2, in which the PRC2 core associates with distinct ancillary subunits such as MTF2 and JARID2, respectively. Both MTF2, present in PRC2.1, and JARID2, present in PRC2.2, play a role in core PRC2 recruitment to target genes in mouse embryonic stem cells (mESCs). However, it remains unclear how these distinct sub-complexes cooperate to establish H3K27me3 domains. Here, we combine a range of Polycomb mutant mESCs with chemical inhibition of PRC2 catalytic activity, to systematically dissect their relative contributions to PRC2 binding to target loci. We find that PRC2.1 and PRC2.2 mediate two distinct paths for recruitment, with mutually reinforced binding. Part of the cross-talk between PRC2.1 and PRC2.2 occurs via their catalytic product H3K27me3, which is bound by the PRC2 core-subunit EED, thereby mediating a positive feedback. Strikingly, removal of either JARID2 or H3K27me3 only has a minor effect on PRC2 recruitment, whereas their combined ablation largely attenuates PRC2 recruitment. This strongly suggests an unexpected redundancy between JARID2 and EED-H3K27me3-mediated recruitment of PRC2. Furthermore, we demonstrate that all core PRC2 recruitment occurs through the combined action of MTF2-mediated recruitment of PRC2.1 to DNA and PRC1-mediated recruitment of JARID2-containing PRC2.2. Both axes of binding are supported by EED-H3K27me3 positive feedback, but to a different degree. Finally, we provide evidence that PRC1 and PRC2 mutually reinforce reciprocal binding. Together, these data disentangle the interdependent and cooperative interactions between Polycomb complexes that are important to establish Polycomb repression at target sites.
2021-09-22 | PXD020684 | Pride
Project description:Polycomb repressive complex (PRC) 2, containing minimally EZH2, EED and Suz12, is the H3 lysine 27 methyltransferase playing pivotal roles in transcriptional regulation. EZH2 is the catalytic subunit, and H3K27me3 activates PRC2 through binding EED to propagate the repressive mark. Cofactor SAM-competitive (SAM-C) PRC2 inhibitors (PRC2is) have been discovered to treat lymphoma and rhabdoid tumors. Here we report the discovery of EED226, a potent and selective PRC2i directly binding to the H3K27me3 pocket of EED. Upon binding, EED226 induces conformational change in EED protein. Interestingly, it inhibits both the basal and the H3K27me3-stimulated PRC2 activities. Furthermore, EED226 selectively pulled down the endogenous PRC2 complex from human cell lysates, specifically modulates H3K27 methylation and target genes similarly as SAM-C PRC2 inhibitors, and effectively regresses human lymphoma xenograft tumor in mouse. More importantly, EED226 potently inhibits the SAM-C inhibitor-resistant PRC2 and synergizes with SAM-C PRC2i in cell proliferation blocking. Together, EED226 is an inhibitor of PRC2 with a novel mechanism and represent a potential complementary strategy for PRC2-targeted cancer therapy.
2017-01-30 | GSE81267 | GEO
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
Project description:Epigenetic memory undergoes drastic reprogramming in intergenerational gamete-to-embryo transition. H3K27me3, a histone mark catalyzed by PRC2 (Polycomb Repressive Complex 2), is an evolutionally conserved histone mark that plays essential roles in stably repressing developmental genes to maintain cell-type-specific programs. In mice, H3K27me3-mediated epigenetic memory, however, undergoes both resetting at classic Polycomb targets and inheritance of broad H3K27me3 domains that mediate noncanonical imprinting (noncanonical H3K27me3 domains) during early embryogenesis. How such erasure and inheritance are achieved simultaneously remains elusive. Here, through temporal profiling of chromatin occupancy, we show that PRC2 associates with H3K27me3 at both Polycomb targets and noncanonical domains in growing oocytes. PRC2 then pre-disassembles and dissociates from chromatin in mature oocytes, before H3K27me3 erasure at Polycomb targets after fertilization. PRC2 reappears at Polycomb targets in blastocysts when H3K27me3 initiates restoration. By contrast, noncanonical H3K27me3 domains persist to blastocysts, where PRC2 rapidly rebinds by the end of 1-cell embryos until blastocysts. Mechanistically, we found that such noncanonical PRC2 action is regulated by EZHIP, a PRC2 inhibitory factor. By doing so, EZHIP plays a key role in both H3K27me3 erasure and intergenerational inheritance, as well as H3K27me3 re-establishment. Ezhip is highly translated around fertilization, which strongly restricts PRC2 activity, leading to gradual decrease of H3K27me3. Upon knockout of maternal Ezhip, PRC2 becomes hyperactive, binds promiscuously in the genome and deposits widespread H3K27me3. Consequently, H3K27me3 allelic bias and noncanonical imprinting, including imprinted X chromosome inactivation, are impaired. Unexpectedly, the widespread ectopic H3K27me3 paradoxically causes de-repression of H3K27me3 targets, possibly due to dilution of H3K27me3 effectors. Loss of Ezhip further attenuates H3K27me3 restoration at Polycomb targets during peri-implantation, and leads to gene dysregulation and sub-lethality after implantation. Taken together, we uncover PRC2 noncanonical chromatin association during the parental-to-embryonic transition and identify Ezhip as a crucial regulator for both erasure and inheritance of intergenerational epigenetic memories.
2025-11-18 | GSE289282 | GEO
Project description:Epigenetic memory undergoes drastic reprogramming in intergenerational gamete-to-embryo transition. H3K27me3, a histone mark catalyzed by PRC2 (Polycomb Repressive Complex 2), is an evolutionally conserved histone mark that plays essential roles in stably repressing developmental genes to maintain cell-type-specific programs. In mice, H3K27me3-mediated epigenetic memory, however, undergoes both resetting at classic Polycomb targets and inheritance of broad H3K27me3 domains that mediate noncanonical imprinting (noncanonical H3K27me3 domains) during early embryogenesis. How such erasure and inheritance are achieved simultaneously remains elusive. Here, through temporal profiling of chromatin occupancy, we show that PRC2 associates with H3K27me3 at both Polycomb targets and noncanonical domains in growing oocytes. PRC2 then pre-disassembles and dissociates from chromatin in mature oocytes, before H3K27me3 erasure at Polycomb targets after fertilization. PRC2 reappears at Polycomb targets in blastocysts when H3K27me3 initiates restoration. By contrast, noncanonical H3K27me3 domains persist to blastocysts, where PRC2 rapidly rebinds by the end of 1-cell embryos until blastocysts. Mechanistically, we found that such noncanonical PRC2 action is regulated by EZHIP, a PRC2 inhibitory factor. By doing so, EZHIP plays a key role in both H3K27me3 erasure and intergenerational inheritance, as well as H3K27me3 re-establishment. Ezhip is highly translated around fertilization, which strongly restricts PRC2 activity, leading to gradual decrease of H3K27me3. Upon knockout of maternal Ezhip, PRC2 becomes hyperactive, binds promiscuously in the genome and deposits widespread H3K27me3. Consequently, H3K27me3 allelic bias and noncanonical imprinting, including imprinted X chromosome inactivation, are impaired. Unexpectedly, the widespread ectopic H3K27me3 paradoxically causes de-repression of H3K27me3 targets, possibly due to dilution of H3K27me3 effectors. Loss of Ezhip further attenuates H3K27me3 restoration at Polycomb targets during peri-implantation, and leads to gene dysregulation and sub-lethality after implantation. Taken together, we uncover PRC2 noncanonical chromatin association during the parental-to-embryonic transition and identify Ezhip as a crucial regulator for both erasure and inheritance of intergenerational epigenetic memories.
2025-11-18 | GSE289641 | GEO