 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 08, 2022 |
| Title |
(RNA-seq) USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
|
| |
|
| Overall design |
RNA-seq analysis of wild-type or USP7-KO DLD1 cells. DOX treatment for 1, 3, or 9 days was carried out to rescue USP7 expression.
contributor: Erasmus Genomics CTU
|
| |
|
| Contributor(s) |
Sijm A, Atlasi Y, van der Knaap JA, van der Meer JW, Chalkley GE, Bezstarosti K, Dekkers DH, Doff WA, Ozgur Z, van IJcken WF, Demmers JA, Verrijzer CP |
| Citation(s) |
36332031 |
| |
| Submission date |
Jan 04, 2022 |
| Last update date |
Nov 09, 2022 |
| Contact name |
Yaser Atlasi |
| E-mail(s) |
y.atlasi@qub.ac.uk
|
| Organization name |
Queen's University Belfast
|
| Department |
patrick G Johnston Centre for Cancer research
|
| Street address |
Lisburn Road
|
| City |
Belfast |
| ZIP/Postal code |
BT9 7AE |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (15)
|
|
| This SubSeries is part of SuperSeries: |
| GSE193020 |
USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3 |
|
| Relations |
| BioProject |
PRJNA794141 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE193019_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BW) |
| GSE193019_deseq2_results.xlsx |
9.9 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...