Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression (RNA-Seq)
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PROVIDER: PRJNA489755 | ENA |
REPOSITORIES: ENA
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Project description:Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression
| PRJNA489732 | ENA
Project description:The Polycomb system modifies chromatin and plays an essential role in repressing gene expression to control normal mammalian development. However, the components and mechanisms that define how Polycomb protein complexes achieve this remain enigmatic. Here we use combinatorial genetic perturbation coupled with quantitative genomics to discover the central determinants of Polycomb-mediated gene repression in mouse embryonic stem cells. We demonstrate that canonical Polycomb repressive complex 1 (PRC1), which mediates higher order chromatin structures, contributes little to gene repression. Instead, we uncover an unexpectedly high degree of synergy between variant PRC1 complexes which is fundamental to gene repression. We further demonstrate that variant PRC1 complexes are responsible for distinct pools of H2A monoubiquitylation that are associated with repression of Polycomb target genes and silencing during X-chromosome inactivation. Together, these discoveries reveal a new variant PRC1-dependent logic for Polycomb-mediated gene repression.
2019-04-26 | GSE119618 | GEO
Project description:The Polycomb system modifies chromatin and plays an essential role in repressing gene expression to control normal mammalian development. However, the components and mechanisms that define how Polycomb protein complexes achieve this remain enigmatic. Here we use combinatorial genetic perturbation coupled with quantitative genomics to discover the central determinants of Polycomb-mediated gene repression in mouse embryonic stem cells. In contrast to prevailing views, we demonstrate that canonical Polycomb repressive complex 1 (PRC1), which mediates higher order chromatin structures, contributes little to gene repression. Instead, we uncover an unexpectedly high degree of synergy between variant PRC1 complexes which is fundamental to gene repression. We further demonstrate that variant PRC1 complexes are responsible for distinct pools of H2A monoubiquitylation that are associated with repression of Polycomb target genes and silencing during X-chromosome inactivation. Together, these discoveries reveal a new variant PRC1-dependent logic for Polycomb-mediated gene repression.
2019-04-26 | GSE119619 | GEO
Project description:Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression (ChIP-Seq)
| PRJNA489754 | ENA
Project description: Not available
| S-EPMC6561741 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-04-25 | GSE119620 | GEO
Project description:Polycomb Repressive Complexes (PRC), and their chromatin-modifying activities, are essential for the correct regulation of gene expression during cellular differentiation and development. Although their role in transcriptional repression is well described, a detailed molecular understanding of their complex assembly and enzymatic activity has been lacking. We therefore set out to characterize the relationship between PRC1 complex composition and its ability to catalyse H2AK119ub1 for one of the most abundant PRC1 complexes in embryonic stem cells, PCGF1-PRC1. Biochemical reconstitution of the PCGF1-PRC1 complex revealed that RYBP/YAF2 was essential for robust enzymatic activity of the complex. Using calibrated ChIP-seq for H2AK119ub1, we identify that RYBP-dependent PRC1 activity has a widespread role in shaping H2AK119ub1 levels genome-wide in mouse embryonic stem cells. Furthermore, these H2AK119ub1 levels stimulate PRC2 activity as part of an activity-based feedback loop, which we demonstrate is required for maintenance of transcriptional repression. Together, these observations uncover complex-based principles for PRC1 assembly and activity, and further our understanding of Polycomb domain function. This SuperSeries is composed of the SubSeries listed below.
2016-10-05 | GSE83135 | GEO
Project description:The heterogeneous nature of mammalian PRC1 complexes has hindered our understanding of their biological functions. Here, we present a comprehensive proteomic and genomic analysis that uncovered six major groups of PRC1 complexes each containing a distinct PCGF subunit, a RING1A/B ubiquitin ligase, and a unique set of associated polypeptides. These PRC1 complexes differ in their genomic localization and only a small subset co-localize with H3K27me3. Further biochemical dissection revealed that the six PCGFM-bM-^@M-^SRING1A/B combinations form multiple complexes through association with RYBP or its homolog YAF2, which prevents the incorporation of other canonical PRC1 subunits such as CBX, PHC and SCM. Although both RYBP/YAF2- and CBX/PHC/SCM-containing complexes compact chromatin, only RYBP stimulates the activity of RING1B toward H2AK119ub1, suggesting a central role in PRC1 function. Knockdown of RYBP in ES cells compromised their ability to form embryoid bodies, likely because of defects in cell proliferation and maintenance of H2AK119ub1 level. ChIP-seq experiments of different PRC1 components were performed either on HA-tagged transgenic stable 293T-REx lines or on endogenous subunits using specific antibodies.
2012-02-09 | E-GEOD-34774 | biostudies-arrayexpress
Project description:Polycomb Repressive Complexes (PRC), and their chromatin-modifying activities, are essential for the correct regulation of gene expression during cellular differentiation and development. Although their role in transcriptional repression is well described, a detailed molecular understanding of their complex assembly and enzymatic activity has been lacking. We therefore set out to characterize the relationship between PRC1 complex composition and its ability to catalyse H2AK119ub1 for one of the most abundant PRC1 complexes in embryonic stem cells, PCGF1-PRC1. Biochemical reconstitution of the PCGF1-PRC1 complex revealed that RYBP/YAF2 was essential for robust enzymatic activity of the complex. Using calibrated ChIP-seq for H2AK119ub1, we identify that RYBP-dependent PRC1 activity has a widespread role in shaping H2AK119ub1 levels genome-wide in mouse embryonic stem cells. Furthermore, these H2AK119ub1 levels stimulate PRC2 activity as part of an activity-based feedback loop, which we demonstrate is required for maintenance of transcriptional repression. Together, these observations uncover complex-based principles for PRC1 assembly and activity, and further our understanding of Polycomb domain function.
2016-10-05 | GSE83094 | GEO
Project description:Polycomb Repressive Complexes (PRC), and their chromatin-modifying activities, are essential for the correct regulation of gene expression during cellular differentiation and development. Although their role in transcriptional repression is well described, a detailed molecular understanding of their complex assembly and enzymatic activity has been lacking. We therefore set out to characterize the relationship between PRC1 complex composition and its ability to catalyse H2AK119ub1 for one of the most abundant PRC1 complexes in embryonic stem cells, PCGF1-PRC1. Biochemical reconstitution of the PCGF1-PRC1 complex revealed that RYBP/YAF2 was essential for robust enzymatic activity of the complex. Using calibrated ChIP-seq for H2AK119ub1, we identify that RYBP-dependent PRC1 activity has a widespread role in shaping H2AK119ub1 levels genome-wide in mouse embryonic stem cells. Furthermore, these H2AK119ub1 levels stimulate PRC2 activity as part of an activity-based feedback loop, which we demonstrate is required for maintenance of transcriptional repression. Together, these observations uncover complex-based principles for PRC1 assembly and activity, and further our understanding of Polycomb domain function.
2016-10-05 | GSE83093 | GEO