PXD047401

PXD047401 is an original dataset announced via ProteomeXchange.

Title	Specific cPRC1 complexes are co-opted to mediate oncogenic gene repression in H3K27M-mutant 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 the enzymatic activity of the complex. Paradoxically, PRC2 histone methyltransferase activity is essential in for oncogenic gene repression in DMG tumour cells though downstream molecular mechanisms that are poorly understood. Here, we discover that this oncogenic gene repression is mediated by specific canonical PRC1 (cPRC1) formations containing CBX4. By combining CRISPR screening, biochemical and chromatin mapping approaches with functional perturbations we show that cPRC1 complexes containing CBX4-cPRC1 is co-opted to drive repression downstream of H3K27me3 in DMG cells. Remarkably, the altered H3K27me3 landscape characteristic of H3K27M-mutant DMG rewires the distribution of distinct cPRC1 complexes such that CBX4-cPRC1 accumulates at sites of H3K27me3 while other cPRC1 formations are reduced. Despite CBX4-cPRC1 accounting for less than 5% all cPRC1 H3K27M-mutant DMG, it acts as the predominant repressor of (Polycomb target) neural differentiation genes in this setting. Our findings link the altered distribution of H3K27me3 with imbalances of CBX-cPRC1 functions and consequent oncogenic gene repression, revealing new disease mechanisms and potential therapeutic opportunities in this incurable childhood brain tumour.
HostingRepository	PRIDE
AnnounceDate	2025-06-24
AnnouncementXML	Submission_2025-06-24_06:54:43.164.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pascal Jansen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-30 06:16:29	ID requested
⏵ 1	2025-06-24 06:54:43	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: glioma, epigenetics,PRC2

Michiel Vermeulen
contact affiliation	Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, 6525 GA Nijmegen, The Netherlands
contact email	michiel.vermeulen@ru.nl
lab head
Pascal Jansen
contact affiliation	Radboud University
contact email	p.jansen@science.ru.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/2025/06/PXD047401

PRIDE project URI

• PRIDE
  1. PXD047401
     1. Label: PRIDE project
     2. Name: Specific cPRC1 complexes are co-opted to mediate oncogenic gene repression in H3K27M-mutant diffuse midline glioma.