Polycomb repression works without Siesta [ChIP]
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PROVIDER: PRJNA1291712 | ENA |
REPOSITORIES: ENA
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Project description:Polycomb repression works without Siesta [TRIP]
| PRJNA1292739 | ENA
Project description:Polycomb group proteins are essential for epigenetic repression of developmental genes. They act as multi-subunit complexes whose biochemical functions are yet to be fully characterised. One of the complexes, canonical Polycomb Repressive Complex 1 (PRC1), acts as an E3 ligase, depositing a single ubiquitin molecule on histone H2A. It can also bind to histone H3 tri-methylated at lysine 27 (H3K27me3), which is critical to propagate the repressed state of regulated genes epigenetically. The RING1 subunit of PRC1, responsible for the ubiquitin ligase activity, forms other complexes. These complexes can ubiquitylate H2A but cannot bind H3K27me3. It was proposed that H2A ubiquitylation is an essential part of the repressive mechanism and that variant RING1 complexes evolved from ancestral canonical PRC1 to diversify the Polycomb system and enable the evolution of vertebrate-specific traits. However, systematic tracing of genes encoding subunits of distinct variant RING1 complexes argues that these complexes appeared early in animal evolution and likely had functions unrelated to epigenetic repression. To address this problem, we leveraged the power of Drosophila genetics to discover that canonical PRC1 and variant RING1 complexes monoubiquitylate H2A across distinct genomic regions. We found that the sole Drosophila PCGF protein specific for variant RING1 complexes, which we named Siesta, is not required for epigenetic repression of homeotic genes, but controls larval locomotion independently of H2A ubiquitylation. Exploiting the division of labour between PRC1 and Siesta-RING1 complexes, we employed thousands of reporters integrated in parallel to conclude that H2A ubiquitylation has no major repressive effect on transcription. We propose that variant RING1 complexes are not part of the Polycomb regulatory system and that the current PRC1 nomenclature needs revision.
2025-07-17 | GSE302678 | GEO
Project description:Polycomb group proteins are essential for epigenetic repression of developmental genes. They act as multi-subunit complexes whose biochemical functions are yet to be fully characterised. One of the complexes, canonical Polycomb Repressive Complex 1 (PRC1), acts as an E3 ligase, depositing a single ubiquitin molecule on histone H2A. It can also bind to histone H3 tri-methylated at lysine 27 (H3K27me3), which is critical to propagate the repressed state of regulated genes epigenetically. The RING1 subunit of PRC1, responsible for the ubiquitin ligase activity, forms other complexes. These complexes can ubiquitylate H2A but cannot bind H3K27me3. It was proposed that H2A ubiquitylation is an essential part of the repressive mechanism and that variant RING1 complexes evolved from ancestral canonical PRC1 to diversify the Polycomb system and enable the evolution of vertebrate-specific traits. However, systematic tracing of genes encoding subunits of distinct variant RING1 complexes argues that these complexes appeared early in animal evolution and likely had functions unrelated to epigenetic repression. To address this problem, we leveraged the power of Drosophila genetics to discover that canonical PRC1 and variant RING1 complexes monoubiquitylate H2A across distinct genomic regions. We found that the sole Drosophila PCGF protein specific for variant RING1 complexes, which we named Siesta, is not required for epigenetic repression of homeotic genes, but controls larval locomotion independently of H2A ubiquitylation. Exploiting the division of labour between PRC1 and Siesta-RING1 complexes, we employed thousands of reporters integrated in parallel to conclude that H2A ubiquitylation has no major repressive effect on transcription. We propose that variant RING1 complexes are not part of the Polycomb regulatory system and that the current PRC1 nomenclature needs revision.
2025-07-17 | GSE302873 | 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:Macromolecular interactions dictate Polycomb-mediated epigenetic repression [ChIP-seq]
| PRJNA1133036 | ENA
Project description:The mammalian SWI/SNF, or BAF complex, has a conserved and direct role in antagonizing polycomb-mediated repression. Yet, BAF also promotes repression by polycomb in stem cells and cancer. How BAF both antagonizes and promotes polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-polycomb axis in embryonic stem cells on short timescales. We report that rapid BAF depletion redistributes PRC1 and PRC2 complexes from highly occupied domains, like Hox clusters, to weakly occupied sites normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features, and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 & PRC2 we identify a conventional role for BAF in polycomb-mediated repression, in addition to global polycomb redistribution. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis.
2021-06-11 | GSE173550 | GEO
Project description:PR-DUB safeguards Polycomb repression through restricting H2AK119ub1 [ChIP-seq]
| PRJNA773660 | ENA
Project description:Polycomb group proteins play a critical role in silencing transcription during development. It is commonly proposed that Polycomb dependent changes in genome folding, which compact chromatin, contribute directly to repression by blocking binding of activating complexes. Recently, it has also been argued that liquid-liquid demixing of Polycomb proteins facilitates this compaction and repression by phase-separating target genes into a membraneless compartment. To test these models, we utilized Optical Reconstruction of Chromatin Architecture (ORCA) to trace the Hoxa gene cluster, a canonical Polycomb target, in thousands of single cells. Across multiple cell types, we find that Polycomb-bound chromatin frequently explores decompact states and partial mixing with neighboring chromatin, while remaining uniformly repressed, challenging the repression-by-compaction or phase-separation models. Using polymer simulations, we show that these observed flexible ensembles can be explained by “spatial feedback”: transient contacts that contribute to propagation of the epigenetic state, (epigenetic memory) without inducing a globular organization.
2024-02-08 | GSE237501 | 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:PR-DUB safeguards Polycomb repression through restricting H2AK119ub1
| PRJNA773657 | ENA