A Central Role for PRC1 in Shaping the 3D Nuclear Landscape
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ABSTRACT:
PROVIDER: PRJNA556587 | ENA |
REPOSITORIES: ENA
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Project description:1. Loss of RING1B substantially disrupts nuclear architecture. 2. PRC1 mediated looping can occur at a Mb scale and is independent of CTCF. 3. Polycomb mediated looping is driven by canonical PRC1 complexes. 4. Trimeric PRC1-mediated interactions occur in vitro and in vivo. 5. Gene up-regulation does not directly lead to the loss of PRC1 loops.
2019-12-15 | GSE134826 | GEO
Project description:Polycomb group (PcG) proteins silence gene expression by chemically and physically modifying chromatin. A subset of PcG target loci are compacted and cluster in the nucleus; a conformation that is thought to contribute to gene silencing. However, how these interactions influence gross nuclear organization and their relationship with transcription remains poorly understood. Here we examine the role of Polycomb-repressive complex 1 (PRC1) in shaping 3D genome organization in mouse embryonic stem cells (mESCs). Using a combination of imaging and Hi-C analyses, we show that PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at a megabase scale. Impairment of PRC1 enzymatic activity does not directly disrupt these interactions. We demonstrate that PcG targets coalesce in vivo, and that developmentally induced expression of one of the target loci disrupts this spatial arrangement. Finally, we show that transcriptional activation and the loss of PRC1-mediated interactions are separable events. These findings provide important insights into the function of PRC1, while highlighting the complexity of this regulatory system.
| S-EPMC7328521 | biostudies-literature
Project description:The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how it selects its target genes is poorly understood and whether its histone modifying activities are required for transcriptional repression remains controversial. Here, we directly test the requirement for PRC1 catalytic activity in Polycomb system function. To achieve this, we develop a new inducible mutation system in embryonic stem cells that completely removes PRC1 catalytic activity. Using this system, we demonstrate that catalysis by PRC1 is important for Polycomb chromatin domain formation and long-range chromatin interactions. Furthermore, we show that variant PRC1 complexes with DNA-binding activities occupy target sites independently of Polycomb chromatin domain formation, providing a putative mechanism for Polycomb target site selection. Finally, we discover that Polycomb-mediated gene repression requires PRC1 catalytic activity. Together these discoveries provide compelling new evidence that PRC1 catalysis is central to Polycomb system function and gene regulation.
2020-01-08 | GSE132753 | GEO
Project description:The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how it selects its target genes is poorly understood and whether its histone modifying activities are required for transcriptional repression remains controversial. Here, we directly test the requirement for PRC1 catalytic activity in Polycomb system function. To achieve this, we develop a new inducible mutation system in embryonic stem cells that completely removes PRC1 catalytic activity. Using this system, we demonstrate that catalysis by PRC1 is important for Polycomb chromatin domain formation and long-range chromatin interactions. Furthermore, we show that variant PRC1 complexes with DNA-binding activities occupy target sites independently of Polycomb chromatin domain formation, providing a putative mechanism for Polycomb target site selection. Finally, we discover that Polycomb-mediated gene repression requires PRC1 catalytic activity. Together these discoveries provide compelling new evidence that PRC1 catalysis is central to Polycomb system function and gene regulation.
2020-01-08 | GSE132752 | GEO
Project description:The Polycomb repressive system is an essential chromatin-based regulator of gene expression. Despite being extensively studied, how it selects its target genes is poorly understood and whether its histone modifying activities are required for transcriptional repression remains controversial. Here, we directly test the requirement for PRC1 catalytic activity in Polycomb system function. To achieve this, we develop a new inducible mutation system in embryonic stem cells that completely removes PRC1 catalytic activity. Using this system, we demonstrate that catalysis by PRC1 is important for Polycomb chromatin domain formation and long-range chromatin interactions. Furthermore, we show that variant PRC1 complexes with DNA-binding activities occupy target sites independently of Polycomb chromatin domain formation, providing a putative mechanism for Polycomb target site selection. Finally, we discover that Polycomb-mediated gene repression requires PRC1 catalytic activity. Together these discoveries provide compelling new evidence that PRC1 catalysis is central to Polycomb system function and gene regulation.
2020-01-08 | GSE132751 | GEO
Project description:PRC1 catalytic activity is central to Polycomb system function.
| PRJNA548920 | ENA
Project description:PRC1 catalytic activity is central to Polycomb system function. [CaptureC ]
| PRJNA548921 | ENA
Project description:PRC1 catalytic activity is central to Polycomb system function. [ChIP]
| PRJNA548922 | ENA
Project description:PRC1 catalytic activity is central to Polycomb system function. [RNA]
| PRJNA548923 | ENA
Project description:Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) are highly conserved epigenetic factors that collaborate at multiple levels to maintain their target genes in a repressed state. However, recent reports suggest that PRC1 binds a subset of active promoters and enhancers devoid of the PRC2-mediated H3K27me3 repressive mark in both Drosophila and mammals. Here, we characterize the 3D epigenome of Drosophila Eye-antennal imaginal discs (EDs) and identify a large set of PRC1-bound promoters and enhancers that show preferential interactions in 3D. These PRC1-centered contacts are generally not pre-formed in embryos and coincide with increased PRC1 binding at the larval stage, a concomitant increase in expression during development and mis-regulation in PRC1 mutants. A detailed analysis of the dachshund locus indicates that PRC1-anchored chromatin loops are not only repressive structures, but might also be required for gene activation. Finally, a meta-analysis of RING1B binding profiles and 3D contacts during mouse neural differentiation suggests that this function might be conserved in mammals. These data suggest that, in addition to its known function in gene silencing, PRC1 binding to enhancers and promoters favors stage-specific 3D contacts to facilitate transcription of key developmental genes.
2020-01-12 | GSE126985 | GEO