PXD051616

PXD051616 is an original dataset announced via ProteomeXchange.

Title	USP7, a protein involved in Hao-Fountain syndrome, controls neuronal differentiation via BCOR-ncPRC1.1
Description	Pathogenic variants in the ubiquitin-specific protease 7 (USP7) gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, which of its pleiotropic substrates are relevant for neurodevelopment is undetermined. Here, we present a combination of quantitative proteomics, transcriptomics and epigenomics to define the USP7 regulatory circuitry during neurodifferentiation. USP7 activity is required for the transcriptional programs that direct differentiation of embryonic stem cells to neural stem cells, and neuronal differentiation of SHSY5Y neuroblastoma cells. USP7 controls the dosage of the Polycomb H2AK119ub1 ubiquitin ligases ncPRC1.1 and ncPRC1.6. Loss-of-function experiments revealed that BCOR-ncPRC1.1, but not ncPRC1.6, is a key effector of USP7-dependent neuronal differentiation. Indeed, BCOR-ncPRC1.1 mediates the majority of USP7-dependent gene regulation during this process. Besides providing a detailed map of the USP7 regulome during neurodifferentiation, our results suggest that USP7- and ncPRC1.1-associated neurodevelopmental disorders involve dysregulation of a common epigenetic network.
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-07_20:38:06.337.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	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-21 13:48:32	ID requested
⏵ 1	2025-09-07 20:38:07	announced

Wolf van der Meer J, Larue A, van der Knaap JA, Chalkley GE, Sijm A, Beikmohammadi L, Kozhevnikova EN, van der Vaart A, Tilly BC, Bezstarosti K, Dekkers DHW, Doff WAS, van de Wetering-Tieleman PJ, Lanko K, Barakat TS, Allertz T, van Haren J, Demmers JAA, Atlasi Y, Verrijzer CP, Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR-ncPRC1.1. Genes Dev, 39(5-6):401-422(2025) [pubmed]

10.1101/gad.352272.124;

submitter keyword: USP7, PRM, DIA-MS, label free quantitative proteomics, neuronal differentiation, BCOR, Hao-Fountain syndrome

Jeroen demmers
contact affiliation	Proteomics Center, Erasmus MC
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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/09/PXD051616

PRIDE project URI

• PRIDE
  1. PXD051616
     1. Label: PRIDE project
     2. Name: USP7, a protein involved in Hao-Fountain syndrome, controls neuronal differentiation via BCOR-ncPRC1.1