PXD046064-1

PXD046064 is an original dataset announced via ProteomeXchange.

Title	PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression
Description	Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are mutated in nearly 25% of cancers. To gain insight into the mechanisms by which SWI/SNF mutations drive cancer, we contributed ten rhabdoid tumor (RT) cell lines mutant for SWI/SNF subunit SMARCB1 to a genome-scale CRISPR Cas9 depletion screen performed across 896 cell lines. We identify PHF6 as specifically essential for RT cell survival and demonstrate that dependency on Phf6 extends to Smarcb1-deficient cancers in vivo. As mutations in either SWI/SNF or PHF6 can cause the neurodevelopmental disorder Coffin-Siris syndrome, our findings of a dependency suggest a previously unrecognized functional link. We demonstrate that PHF6 co-localizes with SWI/SNF complexes at promoters, where it is essential for maintenance of an active chromatin state. We show that in the absence of SMARCB1, PHF6 loss disrupts the recruitment and stability of residual SWI/SNF complex members, collectively resulting in the loss of active chromatin at promoters and stalling of RNA Polymerase II progression. Our work establishes a mechanistic basis for the shared syndromic features of SWI/SNF and PHF6 mutations in CSS and the basis for selective dependency on PHF6 in SMARCB1-mutant cancers.
HostingRepository	MassIVE
AnnounceDate	2024-05-30
AnnouncementXML	Submission_2024-05-30_09:52:50.159.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Priya Mittal
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Acetyl; Methyl; Dimethyl; Trimethyl
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-11 07:14:58	ID requested
⏵ 1	2024-05-30 09:52:50	announced

no publication

submitter keyword: PHF6, chromatin, SWI/SNF, pediatric cancer, dependency

Charles W M Roberts
contact affiliation	St Jude Childrens Hospital
contact email	charles.roberts@stjude.org
lab head
Priya Mittal
contact affiliation	St. Jude Children�s Research Hospital
contact email	Priya.Mittal@STJUDE.ORG
dataset submitter

MassIVE dataset URI

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://massive.ucsd.edu/v06/MSV000093083/