Proximity-dependent recruitment of Polycomb Repressive Complexes by the lncRNA Airn [ChIP-Seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE220464 | GEO | 2023/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:In the developing mouse embryo, expression of the lncRNA Airn induces gene silencing and recruits Polycomb Repressive Complexes (PRCs) to varying extents over a 15 megabase domain, but the mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture centered around a network of CpG islands occupied by PRCs and SMC1A/Cohesin. Extent of contact with Airn predicts underlying intensity of Polycomb-directed chromatin modifications and Airn-induced changes to chromatin architecture. Deletion of individual CpG islands alternately increase or decrease gene silencing and PRC activity over the domain in a manner predicted by changes in chromatin architecture. We conclude that Airn is a potent repressive lncRNA whose effects are controlled by an equilibratory network of DNA regulatory elements that modulate its frequency of contact with target chromatin.
2023-07-01 | GSE217239 | GEO
Project description:In the developing mouse embryo, expression of the lncRNA Airn induces gene silencing and recruits Polycomb Repressive Complexes (PRCs) to varying extents over a 15 megabase domain, but the mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture centered around a network of CpG islands occupied by PRCs and SMC1A/Cohesin. Extent of contact with Airn predicts underlying intensity of Polycomb-directed chromatin modifications and Airn-induced changes to chromatin architecture. Deletion of individual CpG islands alternately increase or decrease gene silencing and PRC activity over the domain in a manner predicted by changes in chromatin architecture. We conclude that Airn is a potent repressive lncRNA whose effects are controlled by an equilibratory network of DNA regulatory elements that modulate its frequency of contact with target chromatin.
2023-07-01 | GSE217261 | GEO
Project description:In the developing mouse embryo, expression of the lncRNA Airn induces gene silencing and recruits Polycomb Repressive Complexes (PRCs) to varying extents over a 15 megabase domain, but the mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture centered around a network of CpG islands occupied by PRCs and SMC1A/Cohesin. Extent of contact with Airn predicts underlying intensity of Polycomb-directed chromatin modifications and Airn-induced changes to chromatin architecture. Deletion of individual CpG islands alternately increase or decrease gene silencing and PRC activity over the domain in a manner predicted by changes in chromatin architecture. We conclude that Airn is a potent repressive lncRNA whose effects are controlled by an equilibratory network of DNA regulatory elements that modulate its frequency of contact with target chromatin.
2023-07-01 | GSE217823 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin, and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, while inhibition of PRC2 promotes trophoblast fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
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Project description:Polycomb group (PcG) proteins are transcriptional repressors with a central role in the establishment and maintenance of gene expression patterns during development. We have investigated the role of Polycomb Repressive Complexes (PRCs) in hematopoietic stem cells (HSCs) and progenitor populations. We show that mice with loss of function mutations in PRC2 components display enhanced HSC/progenitor population activity, whereas mutations that disrupt PRC1 or PhoRC are associated with HSC/progenitor cell defects. Since the hierarchical model of PRC action would predict synergistic effects of PRC1 and PRC2 mutation, these opposing effects suggest this model does not hold true in HSC/progenitor cells. To investigate the molecular targets of each complex in HSC/progenitor cells, we measured genome-wide expression changes associated with PRC-deficiency, and identified transcriptional networks that are differentially regulated by PRC1 and PRC2. These studies provide new insights into the mechanistic interplay between distinct PRCs and have important implications for approaching PcG proteins as therapeutic targets. Total RNA obtained from foetal liver LSK cells from mouse embryos with genes from different polycomb repressive complexes mutated or knocked-out was compared with wild-type samples.
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Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates. Data originating from the LC-MS/MS analysis of the histone PTMs can be consulted via this project.
2022-05-06 | PXD028162 | Pride
Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we apply multi-omics to comprehensively define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Integrating the chromatin-bound proteome and histone modification data sets reveals differences in the relative abundance and activities of distinct chromatin modules, identifying a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin. Single-cell approaches and human blastoid models reveal that PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, and inhibiting PRC2 promotes trophoblast fate induction and cavity formation. Our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
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Project description: Not available
| S-EPMC5310723 | biostudies-literature
Project description:Polycomb group (PcG) proteins are transcriptional repressors with a central role in the establishment and maintenance of gene expression patterns during development. We have investigated the role of Polycomb Repressive Complexes (PRCs) in hematopoietic stem cells (HSCs) and progenitor populations. We show that mice with loss of function mutations in PRC2 components display enhanced HSC/progenitor population activity, whereas mutations that disrupt PRC1 or PhoRC are associated with HSC/progenitor cell defects. Since the hierarchical model of PRC action would predict synergistic effects of PRC1 and PRC2 mutation, these opposing effects suggest this model does not hold true in HSC/progenitor cells. To investigate the molecular targets of each complex in HSC/progenitor cells, we measured genome-wide expression changes associated with PRC-deficiency, and identified transcriptional networks that are differentially regulated by PRC1 and PRC2. These studies provide new insights into the mechanistic interplay between distinct PRCs and have important implications for approaching PcG proteins as therapeutic targets.
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