PXD018381

PXD018381 is an original dataset announced via ProteomeXchange.

Title	Acute BAF perturbation causes immediate changes in chromatin accessibility
Description	Loss-of-function mutations in genes coding for subunits of the large, multifarious BRG1/BRM associated factor (BAF) chromatin remodeling complexes are frequently causative for cancer or developmental diseases1-5. Cells lacking the most frequently mutated subunits like the ATPase SMARCA4 typically exhibit drastic chromatin accessibility changes, especially of important regulatory regions6-12. However, so far it remains unknown how these changes are established over time, and whether they are causative for intra-complex synthetic lethalities abrogating the formation (SMARCC1-SMARCC2)8,13,14 or activity (SMARCA4-SMARCA2)15-17 of BAF complexes. Here, we utilize the dTAG system18 to induce acute degradation of BAF subunits in wild-type and BAF mutant backgrounds and analyze the resulting chromatin accessibility changes with high kinetic resolution. We observe that chromatin alterations are established faster than the duration of one cell cycle and that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in a near-complete loss of chromatin accessibility at BAF-controlled sites, especially at super-enhancers, providing a mechanism for intra-complex synthetic lethalities.
HostingRepository	PRIDE
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-04_13:31:04.603.xml
DigitalObjectIdentifier	http://dx.doi.org/10.6019/PXD018381
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andre Mueller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-06 00:44:28	ID requested
⏵ 1	2021-03-04 13:31:04	announced

Dataset with its publication pending

submitter keyword: BAF complex, mammalian SWI/SNF complex, acute chemical degradation, dTAG knock-in, chromatin remodeling, ATAC-seq, synthetic lethality, chromatin accessibility, kinetics, enhancer

Stefan Kubicek
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3 1090 Vienna, Austria
contact email	skubicek@cemm.oeaw.ac.at
lab head
Andre Mueller
contact affiliation	Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	amueller@cemm.oeaw.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018381
     1. Label: PRIDE project
     2. Name: Acute BAF perturbation causes immediate changes in chromatin accessibility