PXD013102

PXD013102 is an original dataset announced via ProteomeXchange.

Title	Systematic characterization of BAF mutations explains intra-complex synthetic lethalities
Description	Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers.
HostingRepository	PRIDE
AnnounceDate	2019-08-01
AnnouncementXML	Submission_2019-08-01_04:09:02.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD013102
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Peter Májek
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Phospho; Methyl; TMT6plex; Oxidation; Acetyl; Carbamidomethyl
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-15 04:41:29	ID requested
⏵ 1	2019-08-01 04:09:03	announced

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: BAF complex, mammalian SWI/SNF complex, chromatin remodeling, interaction proteomics, ATAC-seq, transcriptomics, synthetic lethality, chromatin accessibility, chromatin binding

Stefan Kubicek
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Christian Doppler Laboratory for Chemical Epigenetics and Anti-Infectives Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria
contact email	SKubicek@cemm.oeaw.ac.at
lab head
Peter Májek
contact affiliation	CeMM, Reserach Center for Molecular Medicine
contact email	pmajek@cemm.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013102
     1. Label: PRIDE project
     2. Name: Systematic characterization of BAF mutations explains intra-complex synthetic lethalities