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USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3 [ChIP-seq]

ABSTRACT: USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3 [ChIP-seq]

PROVIDER: PRJNA899892 | ENA |

REPOSITORIES: ENA

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(RNA-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

Project description:Ubiquitin-specific protease 7 (USP7) has been implicated in cancer progression and neurodevelopment. However, its molecular targets remain poorly characterized. We combined quantitative proteomics, transcriptomics, and epigenomics to define the core USP7 network. Our multi-omics analysis reveals USP7 as a control hub that links genome regulation, tumor suppression, and histone H2A ubiquitylation (H2AK119ub1) by noncanonical Polycomb-repressive complexes (ncPRC1s). USP7 strongly stabilizes ncPRC1.6 and, to a lesser extent, ncPRC1.1. Moreover, USP7 represses expression of AUTS2, which suppresses H2A ubiquitylation by ncPRC1.3/5. Collectively, these USP7 activities promote the genomic deposition of H2AK119ub1 by ncPRC1, especially at transcriptionally repressed loci. Notably, USP7-dependent changes in H2AK119ub1 levels are uncoupled from H3K27me3. Even complete loss of the PRC1 catalytic core and H2AK119ub1 has only a limited effect on H3K27me3. Besides defining the USP7 regulome, our results reveal that H2AK119ub1 dosage is largely disconnected from H3K27me3.

2022-11-08 | GSE193019 | GEO

(ChIP-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

2022-11-08 | GSE193014 | GEO

(ChIP-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

2022-11-08 | GSE193013 | GEO

USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3 [ChIP-seq]

2022-11-12 | GSE217658 | GEO

USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

Project description:USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

| PRJNA794139 | ENA

(RNA-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

Project description:(RNA-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

| PRJNA794141 | ENA

(ChIP-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

Project description:(ChIP-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

| PRJNA794132 | ENA

(ChIP-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

Project description:(ChIP-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3

| PRJNA794133 | ENA

USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3.

| S-EPMC9635827 | biostudies-literature

Multi-omics characterization of the USP7 regulatory circuitry reveals control of H2AK119ub1 dosage uncoupled from H3K27me3 .

Project description:Ubiquitin-specific protease 7 (USP7) has been implicated in multiple cellular and developmental pathways. However, its molecular network remains poorly defined. We combined quantitative proteomics, transcriptomics and epigenomics to define the core USP7 regulome. We found that USP7 forms a regulatory hub, linking processes involved in the packaging, maintenance and expression of the genome. Further analysis revealed that USP7 regulates non-canonical Polycomb repressive complexes 1 (ncPRC1s) but affects neither canonical PRC1s nor PRC2s. By stabilizing key subunits of PRC1.6 and to a lesser extend PRC1.1, USP7 acts as a rheostat that modulates the global level of H2AK119ub11. Unexpectedly, changes in the genomic deposition of H2AK119ub11 are uncoupled from H3K27me3, challenging prevalent models for Polycomb repression. Indeed, a complete loss of PRC1 and H2AK119ub1 has only a highly restricted effect on H3K27me3. Besides defining the organizational principles of the USP7 regulome, our results reveal selective control of H2AK119ub1 dosage that is disconnected from H3K27me3.

2023-03-11 | PXD030707 | Pride

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