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Genome-wide maps of chromatin state in A375 cells or in normal or USP7 knockdown A375 cells .

ABSTRACT: ChIP-seq experiments were performed in normal or USP7 knockdown A375 cells with specific antibodies against USP7, EZH2, H3K27me3 and H2BK120ub1. Consistent with our expectations, the analysis of ChIP-seq data showed that USP7 loss-of-function led to obviously reduction in USP7, EZH2 and H3K27me3 around the USP7-specific peaks, but an upregulation in H2BK120ub1. This study gave us a new understanding that USP7 is required for EZH2 loading and H3K27 trimethylation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133834 | GEO | 2020/05/01

REPOSITORIES: GEO

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Genome-wide maps of chromatin state in A375 cells or in normal or USP7 knockdown A375 cells .

Project description:Genome-wide maps of chromatin state in A375 cells or in normal or USP7 knockdown A375 cells .

| PRJNA552988 | ENA

(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

Novel, Selective Inhibitors of USP7 Uncover Multiple Mechanisms of Antitumor Activity in Vitro and in Vivo

Project description:The human lung tumor cell line, NCI-H526, was treated with DMSO vehicle control or 0.5 µM of the novel small molecule USP7 inhibitor, USP7-797. At 24 and 48 hour time points, cells were harvested and used for RNA-Seq analysis. In order to identify pathways impacted by USP7 (Ubiquitin Specific Peptidase 7) inhibition, we used RNASeq to profile transcriptomic changes in human lung cancer NCI-H526 cells following treatment with the novel, selective USP7 inhibitor, USP7-797, or control DMSO for 24 or 48 hours. USP7 inhibitor treatment resulted in upregulation of a large number of genes normally silenced by the polycomb repressive complex 2 (PRC2). PRC2, whose components include the proteins EZH2, SUZ12 and EED, trimethylates histone H3 at lysine 27 (H3K27me3). Gene set enrichment analysis showed that the top 10 significantly enriched gene sets are all regulated by this pathway. RNA was extracted from approximately 1 million cells using the Allprep DNA/RNA Mini Kit (Qiagen). Whole transcriptome non-stranded libraries were prepared using the TruSeq RNA Library Prep Kit v2 (Illumina). Sequencing was performed on Illumina NovaSeq using paired-end mode, 200 cycles, targeting 40 million reads per sample.

2020-08-17 | GSE151286 | GEO

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

Microarry from Treg with conditional knockout of Usp7

Project description:Microarry from Treg with conditional knockout of Usp7 RNA from three independent samples from FACS sorted CD4+YFP+ Treg of fl-Usp7/Foxp3cre mice, compared to Foxp3cre control (C57BL/6 background).

2015-09-15 | E-GEOD-72988 | biostudies-arrayexpress

YG001: A Usp7-Tip60 pathway regulates early adipogenesis

Project description:USP7, a dominant DUB activity in 3T3-L1 adipocytes and in mouse adipose tissue, increases Tip60 protein levels, and deubiquitinates Tip60 both in intact cells and in vitro. Treatment with a pan deubiquitinase (DUB) inhibitor, or knockdown of USP7, decreases adipogenesis. Transcriptome analysis reveals a common set of cell cycle genes to be co-regulated by both Tip60 and USP7. Knock down of either factor results in impaired mitotic clonal expansion, an early step in adipogenesis. These results therefore reveal deubiquitination of a transcriptional coregulator to be a key mechanism in the regulation of early adipogenesis Mature 3T3-L1 adipocytes were subjected to RNAi-mediated knock down with control(C), USP7(U)- or Tip60(T)-specific oligonucleotides. For this, 4 replicates of differentiated 3T3-L1 cells were transfected with Amaxa technology. Two days after transfection cells were washed twice with PBS twice and lysed in 0.5ml Trizol (Invitrogen). mRNA expression of Tip60 and USP7 was assessed by qRT-PCR. Amplified cRNA samples were labeled with either cy3 or cy5 and put on microarray together with and oppositely labeled common reference sample consisting of cRNA derived from undifferentiated 3T3-L1 cells.

2013-08-28 | E-GEOD-28587 | biostudies-arrayexpress

USP7 cooperates with SCML2 to regulate the activity of PRC1

Project description:In this experiment, we sought to identify the distribution of USP7 on chromatin relative to other PRC1 components ChIP-seq for USP7 in 293T-REx cells

2015-06-10 | E-GEOD-61048 | biostudies-arrayexpress

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