PXD058532

PXD058532 is an original dataset announced via ProteomeXchange.

Title	Specific cPRC1 complexes are co-opted to mediate oncogenic gene repression in diffuse midline glioma
Description	Diffuse midline glioma (DMG) is a fatal childhood brain tumour characterised primarily by mutant histone H3 (H3K27M). H3K27M causes a global reduction in Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 by inhibiting PRC2 enzymatic activity. Paradoxically, PRC2 is essential in DMG tumour cells where residual complex activity is required for oncogenic gene repression, although the molecular mechanisms acting downstream of PRC2 in this context are poorly understood. Here, we’ve discovered this oncogenic gene repression is mediated by specific canonical PRC1 (cPRC1) formations. By combining CRISPR screening, biochemical and chromatin mapping approaches with functional perturbations we show that cPRC1 complexes containing CBX4 and PCGF4 drive oncogenic gene repression downstream of H3K27me3 in DMG cells. Remarkably, the altered H3K27me3 modification landscape characteristic of these tumours rewires the distribution of cPRC1 complexes on chromatin. CBX4 and PCGF4 containing cPRC1 accumulate at sites of H3K27me3 while other cPRC1 formations are displaced. Despite accounting for <5% of cPRC1 complexes in DMG, CBX4/PCGF4-containing complexes predominate as gene repressors. Our findings link the altered distribution of H3K27me3 with imbalanced cPRC1 function, promoting oncogenic gene repression in DMG cells, revealing new disease mechanisms and highlighting potential therapeutic opportunities in this incurable childhood brain tumour.
HostingRepository	PRIDE
AnnounceDate	2025-06-24
AnnouncementXML	Submission_2025-06-24_06:55:06.973.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von Kriegsheim
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	2024-12-03 09:17:27	ID requested
⏵ 1	2025-06-24 06:55:07	announced

10.1016/j.molcel.2025.04.026;

Lagan E, Gannon D, Silva AJ, Bibawi P, Doherty AM, Nimmo D, McCole R, Monger C, Genesi GL, Vanderlinden A, Innes JA, Jones CLE, Yang L, Chen B, van Mierlo G, Jansen PWTC, Pednekar C, Von Kriegsheim A, Wynne K, S, á, nchez-Rivera FJ, Soto-Feliciano YM, Carcaboso AM, Vermeulen M, Oliviero G, Chen CW, Phillips RE, Bracken AP, Brien GL, A specific form of cPRC1 containing CBX4 is co-opted to mediate oncogenic gene repression in diffuse midline glioma. Mol Cell, 85(11):2110-2127.e7(2025) [pubmed]

submitter keyword: interaction proteomics

Gerry Brien
contact affiliation	U o Edinburgh
contact email	gbrien@ed.ac.uk
lab head
Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ed.ac.uk
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/2025/06/PXD058532

PRIDE project URI

• PRIDE
  1. PXD058532
     1. Label: PRIDE project
     2. Name: Specific cPRC1 complexes are co-opted to mediate oncogenic gene repression in diffuse midline glioma