PXD061408

PXD061408 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_07:09:44.873.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD061408
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	2025-03-03 09:26:32	ID requested
⏵ 1	2025-04-28 07:09:45	announced

10.6019/PXD061408;

submitter keyword: Mouse, LFQ, Orbitrap Fusion Lumos

Simon Braun
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

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PRIDE project URI

• PRIDE
  1. PXD061408
     1. Label: PRIDE project
     2. Name: CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly