Histone H2AK119 Mono-Ubiquitination is Essential for Polycomb-Mediated Transcriptional Repression
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ABSTRACT:
PROVIDER: PRJNA553568 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10748900_1.fastq.gz | Fastqsanger.gz | |||
| SRR10748900_2.fastq.gz | Fastqsanger.gz | |||
| SRR10748901_1.fastq.gz | Fastqsanger.gz | |||
| SRR10748901_2.fastq.gz | Fastqsanger.gz | |||
| SRR10748902_1.fastq.gz | Fastqsanger.gz |
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Project description:Polycomb group proteins (PcGs) maintain transcriptional repression to preserve cellular identity in two distinct repressive complexes, PRC1 and PRC2, that modify histones by depositing H2AK119ub1 and H3K27me3, respectively. PRC1 and PRC2 exist in different variants and show a complex regulatory cross-talk. However, the contribution that H2AK119ub1 plays in mediating PcG repressive functions remains largely controversial. Using a fully catalytic inactive RING1B mutant, we demonstrated that H2AK119ub1 deposition is essential to maintain PcG-target gene repression in embryonic stem cells (ESCs). Loss of H2AK119ub1 induced a rapid displacement of PRC2 activity and a loss of H3K27me3 deposition. This preferentially affected PRC2.2 variant with respect to PRC2.1, destabilizing canonical PRC1 activity. Finally, we found that variant PRC1 forms can sense H2AK119ub1 deposition, which contributes to their stabilization specifically at sites where this modification is highly enriched. Overall, our data place H2AK119ub1 deposition as a central hub that mounts PcG repressive machineries to preserve cell transcriptional identity.
| S-EPMC7033561 | biostudies-literature
Project description:The major function of Polycomb group proteins (PcG) is to maintain transcriptional repression to preserve cellular identity. This is exerted by two distinct repressive complexes, PRC1 and PRC2, that modify histones by depositing H2AK119ub1 and H3K27me3, respectively. Both complexes are essential for development and are deregulated in several types of human tumors. PRC1 and PRC2 exist in different variants and show a complex regulatory cross-talk. However, the contribution that H2AK119ub1 plays in mediating PcG repressive functions remains largely controversial. Coupling an inducible system with the expression of a fully catalytic inactive RING1B mutant, we demonstrated that H2AK119ub1 deposition is essential to maintain PcG-target genes repressed in ESC. Loss of H2AK119ub1 induced a rapid displacement of PRC2 activity and a loss of H3K27me3 deposition. This affected both PRC2.1 and PRC2.2 variants and further correlated with a strong displacement and destabilization of canonical PRC1. Finally, we find that variant PRC1 forms can sense H2AK119ub1 deposition, which contributes to their stabilization specifically at sites where this modification is highly enriched. Overall our data place H2AK119ub1 deposition as central hub that mount PcG repressive machineries to preserve cell transcriptional identit
2019-12-26 | GSE134053 | GEO
Project description:Polycomb group (PcG) proteins are critical chromatin regulators for cell fate control. The mono-ubiquitylation on histone H2AK119 (H2AK119ub1) is one of the well-recognized mechanisms for Polycomb Repressive Complex 1 (PRC1)-mediated transcription repression. However, the specific H2AK119 deubiquitylation complex composed by ASX-like proteins (ASXLs) and BAP1 has also been genetically characterized as a Polycomb Repressive complex (PR-DUB). Here we try to provide a rationale for these counterintuitive findings. Through re-examining the genomic distribution of H2AK119ub1, we find that H2AK119ub1 is non-negligibly distributed at non-promoter regions and associated with PRC1 sampling. Upon deletion of Asxl2 in mouse embryonic stem cells (ESCs), H2AK119ub1 is pervasively gained, especially at non-promoter regions, which is associated with increased RING1B occupancy. Meanwhile RING1B is significantly lost from a subset of the target promoters and thereby results in minor derepression in Asxl2-null ESCs. However notably, Asxl2 loss causes aberrant lineage differetiation, similar to PcG mutants. Therefore, our data reconcile seemingly paradoxical roles of PR-DUB on transcription repression and highlight the importance of a balanced H2AK119ub1 dynamics in developmental regulation.
2023-03-31 | GSE186374 | GEO
Project description:Polycomb group (PcG) proteins are critical chromatin regulators for cell fate control. The mono-ubiquitylation on histone H2AK119 (H2AK119ub1) is one of the well-recognized mechanisms for Polycomb Repressive Complex 1 (PRC1)-mediated transcription repression. However, the specific H2AK119 deubiquitylation complex composed by ASX-like proteins (ASXLs) and BAP1 has also been genetically characterized as a Polycomb Repressive complex (PR-DUB). Here we try to provide a rationale for these counterintuitive findings. Through re-examining the genomic distribution of H2AK119ub1, we find that H2AK119ub1 is non-negligibly distributed at non-promoter regions and associated with PRC1 sampling. Upon deletion of Asxl2 in mouse embryonic stem cells (ESCs), H2AK119ub1 is pervasively gained, especially at non-promoter regions, which is associated with increased RING1B occupancy. Meanwhile RING1B is significantly lost from a subset of the target promoters and thereby results in minor derepression in Asxl2-null ESCs. However notably, Asxl2 loss causes aberrant lineage differetiation, similar to PcG mutants. Therefore, our data reconcile seemingly paradoxical roles of PR-DUB on transcription repression and highlight the importance of a balanced H2AK119ub1 dynamics in developmental regulation.
2023-03-31 | GSE186373 | GEO
Project description:Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3) respectively. Compared to H3K27me3, localization and role of H2AK119ub1 is not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation. This SuperSeries is composed of the SubSeries listed below.
2012-06-12 | GSE38650 | GEO
Project description:Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3) respectively. Compared to H3K27me3, localization and role of H2AK119ub1 is not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation. This SuperSeries is composed of the following subset Series: GSE38224: Expression data from Ring1A(-/-);Ring1B(fl/fl);R26::CreERT2 ES cells expressing either of mock, WT or mutant Ring1B construct before or after OHT treatment GSE38504: ChIP-on-chip analysis of Ring1B, Ring1A, H2AK119u1 and H3K27me3 in mouse ES cells Total RNAs were extracted from the respective ES cells, and were subjected to microarray analysis using Affymetrix GeneChip Mouse Genome 430A 2.0 arrays. ChIP on chip analysis was carried out using the Mouse Promoter ChIP-on-chip Microarray Set (G4490A, Agilent, Palo Alto, Calif., USA). MEFs were subjected to ChIP assay using various antibodies. Purified immunoprecipitated and input DNA was subjected to T7 RNA polymerase-based amplification. Labeling, hybridization and washing were carried out according to the Agilent mammalian ChIP-on-chip protocol (ver.9.0). Scanned images were quantified with Agilent Feature Extraction software under standard conditions.
2012-06-11 | E-GEOD-38650 | biostudies-arrayexpress
Project description:Polycomb repressive complex 1 (PRC1) and PRC2 are chromatin regulators maintaining transcriptional repression by depositing H2A mono-ubiquitination (H2Aub) or H3 lysine 27 tri-methylation (H3K27me3), respectively. While PRC1 is known to be required for transcriptional repression, the contribution of H2Aub in the Polycomb repressive system remains unclear in plants. Here, we directly test the requirement of H2Aub for gene repression in Marchantia polymorpha by generating point mutants in H2A that fail to be ubiquitinated by PRC1. These mutants show reduced H3K27me3 levels on the same target sites as mutants in PRC1 subunits MpBMI1 and the homolog MpBMI1L, revealing that PRC1-catalyzed H2Aub is essential for Polycomb system function. Furthermore, we demonstrate that H2Aub contributes to the PRC1-mediated silencing of genes and transposable elements. Together, our data provide evidence that H2Aub plays indispensable roles in the PRC1-initiated repressive system in Marchantia.
2021-08-13 | GSE164394 | GEO
Project description:Polycomb repressive complexes (PRC) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification.
2018-03-31 | GSE112386 | GEO
Project description:Polycomb repressive complexes (PRC) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification.
2018-03-31 | GSE112398 | GEO
Project description:Polycomb repressive complexes (PRC) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification.
2018-03-31 | GSE112400 | GEO