Polycomb repression works without Siesta [TRIP]
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ABSTRACT:
PROVIDER: PRJNA1292739 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Polycomb repression works without Siesta [ChIP]
| PRJNA1291712 | 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 | GSE302873 | 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 | GSE302678 | GEO
Project description:The protein PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation and can play important roles in T cell differentiation. We have generated mice with CD8-specific TrIP deficiency. Here we provide data detailing that activated TrIP KO CD8 T cells display an increased inflammatory transcriptional profile in the absence of TrIP. Consistent with these effects, we also show that knockout of TrIP specifically in CD8 T cells resulted in reduced growth of syngeneic tumors. When characterizing the tumor-infiltrating cells, we found that TrIP KO led to an increase in the number of tumor-infiltrating T cells, as well as a delay in the acquisition of an exhausted phenotype, based on phenotypic and transcriptomic analyses. Finally, our data suggest that TrIP regulates the diversity of T cell clonal responses to tumors, since we observed an increase in the number of distinct T cell clonotypes responding to a tumor neoantigen. Taken together, we show that TrIP intrinsically restricts the CD8 T cell response to tumors, and that targeting TrIP may augment the anti-tumor response in a way that is distinct from established checkpoint therapies.
2025-07-10 | GSE302184 | 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:PR-DUB safeguards Polycomb repression through restricting H2AK119ub1
| PRJNA773657 | 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. 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:RNA interference (RNAi) and Polycomb repression play evolutionarily conserved and often coordinated roles in transcriptional silencing. Here we show that in the protozoan Tetrahymena thermophila, germ line-specific internally eliminated sequences (IES) - many related to transposable elements (TE) - are transcriptionally activated in mutants deficient in the RNAi-dependent Polycomb repression pathway. Mobilization of recently duplicated TE also dramatically increases in these mutants. Importantly, transcriptional silencing and activation of TE-related sequences are accompanied by switching between noncoding RNA (ncRNA) and mRNA production, which can be affected by co-transcriptional processing as well as RNAi and Polycomb repression. We posit that interplay between RNAi and Polycomb repression is a widespread phenomenon, whose ancestral role is epigenetic silencing of TE.
2019-03-01 | GSE118199 | GEO
Project description:RNA interference (RNAi) and Polycomb repression play evolutionarily conserved and often coordinated roles in transcriptional silencing. Here we show that in the protozoan Tetrahymena thermophila, germ line-specific internally eliminated sequences (IES)—many related to transposable elements (TE)—are transcriptionally activated in mutants deficient in the RNAi-dependent Polycomb repression pathway. Mobilization of recently duplicated TE also dramatically increases in these mutants. Importantly, transcriptional silencing and activation of TE-related sequences are accompanied by switching between noncoding RNA (ncRNA) and mRNA production, which can be affected by co-transcriptional processing as well as RNAi and Polycomb repression. We posit that interplay between RNAi and Polycomb repression is a widespread phenomenon, whose ancestral role is epigenetic silencing of TE.
2019-03-01 | GSE118198 | GEO
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 | GSE173499 | GEO