Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-16364
PROVIDER: PRJNA115321 | ENA |
REPOSITORIES: ENA
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Project description:The Polycomb group proteins are repressive chromatin modifiers with essential roles in metazoan development, cellular differentiation and cell fate maintenance. How Polycomb proteins access active chromatin in order to confer transcriptional silencing during lineage transitions remains unclear. Here we show that the Polycomb Repressive Complex 2 (PRC2) component PHF19 binds the active chromatin mark H3K36me3 via its tudor domain. PHF19 associates with the H3K36me3 demethylase NO66, and is required to recruit the PRC2 complex and NO66 to stem cells genes during differentiation, leading to PRC2 mediated H3K27 tri-methylation, loss of H3K36me3 and transcriptional silencing. We propose a model whereby PHF19 functions during ES cell differentiation to transiently bind the H3K36me3 mark via its tudor domain, forming essential contact points that allow recruitment of PRC2 and H3K36me3 demethylase activity to active gene loci during their transition to a Polycomb-repressed state. Examination of PHF19 genome-wide binding in mouse embryonic stem cells
2012-11-17 | E-GEOD-41609 | biostudies-arrayexpress
Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC12 and PRC21, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. To investigate the link between PRC2 and NuA4, and therefore the the link between H4ac an H3K27me3, we perturbed PRC2 both chemically and genetically.The effects on the histone PTMs were measured with LC-MS/MS.
2025-02-25 | PXD048246 | 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.
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:The Polycomb Group Protein Suz12 Is Required for Embryonic Stem Cell Differentiation
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Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC2 and PRC1, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. Interestingly, the EZH2 proxeome included both PRC complexes, while the RNF2 proxeome only identified PRC1 subunits. More than half of the PRC2 proximal proteins are shared with PRC1, revealing the molecular constitution of polycomb chromatin domains. We identified several pluripotency-associated transcription factors, including NANOG, for which we confirmed genomic co-localisation with PRC2. Upon PRC2 disruption, NANOG redistributes to specific sites containing its DNA binding motif. Finally, we compared PRC2 proximal interactomes between naïve mESCs, serum-cultured mESCs and embryoid bodies, altogether providing a comprehensive resource in different cellular contexts that may help to further decipher Polycomb biology.
2025-02-25 | PXD058327 | Pride
Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC2 and PRC1, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. Interestingly, the EZH2 proxeome included both PRC complexes, while the RNF2 proxeome only identified PRC1 subunits. More than half of the PRC2 proximal proteins are shared with PRC1, revealing the molecular constitution of polycomb chromatin domains. We identified several pluripotency-associated transcription factors, including NANOG, for which we confirmed genomic co-localisation with PRC2. Upon PRC2 disruption, NANOG redistributes to specific sites containing its DNA binding motif. Finally, we compared PRC2 proximal interactomes between naïve mESCs, serum-cultured mESCs and embryoid bodies, altogether providing a comprehensive resource in different cellular contexts that may help to further decipher Polycomb biology.
2025-02-25 | PXD047569 | Pride
Project description:Polycomb-like 3 is a PRC2 component that supports embryonic stem cell self-renewal
| PRJNA139349 | ENA
Project description:The Polycomb repressive complexes PRC1 and PRC2 are key mediators of heritable gene silencing in multicellular organisms. Here we characterize AEBP2, a known PRC2 cofactor which, in vitro, has been shown to stimulate PRC2 activity. We show that AEBP2 localises specifically to PRC2 target loci, including the inactive X chromosome. Proteomic analysis confirms that AEBP2 associates exclusively with PRC2 complexes. However, analysis of embryos homozygous for a targeted mutation of Aebp2 unexpectedly revealed a Trithorax phenotype, normally linked to antagonism of Polycomb function. Consistent with this we observe elevated levels of PRC2 mediated histone H3K27 methylation at target loci in Aebp2 mutant embryonic stem cells. We further demonstrate that mutant ES cells assemble atypical hybrid PRC2 sub-complexes, potentially accounting for enhancement of Polycomb activity, and suggesting that AEBP2 normally plays a role in defining the mutually exclusive composition of PRC2 sub-complexes. H3K27me3, SUZ12, and AEBP2 ChIP-Seq in wild-type and AEBP2 KO mouse ESCs, biological replicates, pre-cleared chromatin as input, additionally FS2 ChIP-Seq in cells with FS2 tagged AEBP2, HiSeq2000
2016-08-02 | E-GEOD-83082 | biostudies-arrayexpress
Project description:Polycomb function during oogenesis is required for mouse early embryonic development (2-cell embryos)
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