PXD030707

PXD030707 is an original dataset announced via ProteomeXchange.

Title	Multi-omics characterization of the USP7 regulatory circuitry reveals control of H2AK119ub1 dosage uncoupled from H3K27me3 .
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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:42:13.173.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-04 03:13:21	ID requested
1	2023-03-11 03:37:39	announced
⏵ 2	2023-11-14 08:42:14	announced	2023-11-14: Updated project metadata.

Sijm A, Atlasi Y, van der Knaap JA, Wolf van der Meer J, Chalkley GE, Bezstarosti K, Dekkers DHW, Doff WAS, Ozgur Z, van IJcken WFJ, Demmers JAA, Verrijzer CP, USP7 regulates the ncPRC1 Polycomb axis to stimulate genomic H2AK119ub1 deposition uncoupled from H3K27me3. Sci Adv, 8(44):eabq7598(2022) [pubmed]

submitter keyword: AP-MS, histone H2A ubiquitylation, PRC1, PRC2,PRM, ubiquitin, interactome, USP7, Polycomb

Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus MC, Rotterdam
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030707
     1. Label: PRIDE project
     2. Name: Multi-omics characterization of the USP7 regulatory circuitry reveals control of H2AK119ub1 dosage uncoupled from H3K27me3 .