PXD054392-1

PXD054392 is an original dataset announced via ProteomeXchange.

Title	CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly
Description	The SWI/SNF (or BAF) complex is an essential chromatin remodeler that regulates DNA accessibility at developmental genes and enhancers. SWI/SNF subunits are among the most frequently mutated genes in cancer and neurodevelopmental disorders. These mutations are often heterozygous loss-of-function alleles, indicating a dosage-sensitive role for SWI/SNF subunits in chromatin regulation. However, the molecular mechanisms that regulate SWI/SNF subunit dosage to ensure proper complex assembly remain largely unexplored. We performed a genome-wide CRISPR KO screen, using epigenome editing in mouse embryonic stem cells, and identified Mlf2 and Rbm15 as regulators of SWI/SNF complex activity. First, we show that MLF2, a poorly characterized chaperone protein, regulates a subset of SWI/SNF target genes by promoting its chromatin remodeling activity. Rapid degradation of MLF2 reduces chromatin accessibility at sites that depend on high levels of SWI/SNF binding to maintain open chromatin. Next, we find that RBM15, part of the m6A RNA methylation writer complex, controls m6A modifications on specific SWI/SNF mRNAs to regulate protein levels of these subunits. Misregulation of m6A methylation causes overexpression of core SWI/SNF subunits leading to the assembly of incomplete complexes lacking the catalytic ATPase/ARP subunits. These data indicate that targeting modulators of SWI/SNF complex assembly may offer a potent therapeutic strategy for diseases associated with impaired chromatin remodeling.
HostingRepository	PRIDE
AnnounceDate	2025-04-28
AnnouncementXML	Submission_2025-04-28_07:07:43.784.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD054392
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	alexandre Hainard
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-30 06:45:50	ID requested
⏵ 1	2025-04-28 07:07:44	announced

10.6019/PXD054392;

submitter keyword: Orbitrap fusion Lumos,BAF complex, label-free

Simon M.
contact affiliation	Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Switzerland
contact email	simon.braun@unige.ch
lab head
alexandre Hainard
contact affiliation	Proteomics Core Facility, Faculty of Medicine, University of Geneva
contact email	alexandre.hainard@unige.ch
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/2025/04/PXD054392

PRIDE project URI

• PRIDE
  1. PXD054392
     1. Label: PRIDE project
     2. Name: CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly