PRC1 drives Polycomb-mediated gene repression by controlling transcription initiation and burst frequency [RNA-seq]
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ABSTRACT:
PROVIDER: PRJNA668783 | ENA |
REPOSITORIES: ENA
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Project description:The Polycomb repressive system plays a fundamental role in controlling gene expression during mammalian development. To achieve this, Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) bind target genes and use histone modification-dependent feedback mechanisms to form Polycomb chromatin domains and repress transcription. The interrelatedness of PRC1 and PRC2 activity at these sites has made it difficult to discover the specific components of Polycomb chromatin domains that drive gene repression and to understand mechanistically how this is achieved. Here, by exploiting rapid degron-based approaches and time-resolved genomics we kinetically dissect Polycomb-mediated repression and discover that PRC1 functions independently of PRC2 to counteract RNA polymerase II binding and transcription initiation. Using single-cell gene expression analysis, we reveal that PRC1 acts uniformly within the cell population, and that repression is achieved by controlling transcriptional burst frequency. These important new discoveries provide a mechanistic and conceptual framework for Polycomb-dependent transcriptional control.
2021-07-21 | GSE159399 | GEO
Project description:The Polycomb repressive system plays a fundamental role in controlling gene expression during mammalian development. To achieve this, Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) bind target genes and use histone modification-dependent feedback mechanisms to form Polycomb chromatin domains and repress transcription. The interrelatedness of PRC1 and PRC2 activity at these sites has made it difficult to discover the specific components of Polycomb chromatin domains that drive gene repression and to understand mechanistically how this is achieved. Here, by exploiting rapid degron-based approaches and time-resolved genomics we kinetically dissect Polycomb-mediated repression and discover that PRC1 functions independently of PRC2 to counteract RNA polymerase II binding and transcription initiation. Using single-cell gene expression analysis, we reveal that PRC1 acts uniformly within the cell population, and that repression is achieved by controlling transcriptional burst frequency. These important new discoveries provide a mechanistic and conceptual framework for Polycomb-dependent transcriptional control.
2021-07-21 | GSE159398 | GEO
Project description:PRC1 drives Polycomb-mediated gene repression by controlling transcription initiation and burst frequency
| PRJNA668780 | ENA
Project description:PRC1 drives Polycomb-mediated gene repression by controlling transcription initiation and burst frequency [ChIP-seq]
| PRJNA668782 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-07-19 | GSE159400 | GEO
Project description:Hda1C restricts burst frequency to limit divergent non-coding transcription
| PRJNA704821 | ENA
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:Polycomb-repressive complex 1 (PRC1) has a constraining influence on 3D genome organization, mediating localized and chromosome-wide clustering of target loci. Polycomb-bound regions form transcriptionally repressive chromatin domains independent of topologically associating domains (TADs). Several subunits of PRC1 have the capacity to form biomolecular condensates through liquid-liquid phase separation (LLPS) in vitro and when tagged and over-expressed in cells. Here, we use 1,6 hexandiol (1,6-HD), which disrupts liquid-like condensates, to examine the role of endogenous PRC1 biomolecular condensates on local and chromosome-wide clustering of PRC1-bound loci. Using imaging and chromatin immunoprecipitation combined with deep sequencing (ChIP-seq) analyses, we show that PRC1-mediated localized chromatin compaction and clustering of targeted genomic loci at megabase and tens of megabase scales can be reversibly disrupted by the addition and subsequent removal of 1,6-HD to mouse embryonic stem cells (mESCs). Decompaction and dispersal of polycomb domains and clusters cannot be solely attributable to the reduction of PRC1 binding following 1,6-HD treatment as the addition of 2,5-HD has similar effects despite this alcohol not perturbing PRC1-mediated clustering, at least at the sub-megabase and megabase scales. These results suggest that weak, hydrophobic interactions between PRC1 molecules characteristic of liquid condensates do have a role in polycomb-mediated genome organization.
2023-02-13 | GSE224930 | GEO