Similar Datasets
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.
| S-EPMC6561741 | biostudies-literature
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: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:Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression
| PRJNA489732 | ENA
Project description:Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression (ChIP-Seq)
| PRJNA489754 | ENA
Project description:Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression (RNA-Seq)
| PRJNA489755 | ENA
Project description:Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors that are essential for normal gene regulation during development. However, how these systems function to achieve transcriptional regulation remains very poorly understood. Here, we discover that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3 lysine 27 trimethylation (H3K27me3). Without normal histone modification-dependent communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode, rendering target genes susceptible to inappropriate gene expression signals. This suggests that activity-based communication and histone modification-dependent thresholds create a localized form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.
| S-EPMC5065315 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-07-19 | GSE159400 | GEO
Project description:The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood. Here we demonstrate a critical role for the PRC2 cofactor Jarid2 in mediating the interaction of PRC2 with H2AK119u1. We identify a ubiquitin interaction motif at the amino-terminus of Jarid2, and demonstrate that this domain facilitates PRC2 localization to H2AK119u1 both in vivo and in vitro. Our findings ascribe a critical function to Jarid2 and define a key mechanism that links PRC1 and PRC2 in the establishment of Polycomb domains.
| S-EPMC5133711 | biostudies-literature
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