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PXD018381

PXD018381 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAcute BAF perturbation causes immediate changes in chromatin accessibility
DescriptionLoss-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.
HostingRepositoryPRIDE
AnnounceDate2021-03-04
AnnouncementXMLSubmission_2021-03-04_13:31:04.603.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD018381
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterAndre Mueller
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-06 00:44:28ID requested
12021-03-04 13:31:04announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: BAF complex, mammalian SWI/SNF complex, acute chemical degradation, dTAG knock-in, chromatin remodeling, ATAC-seq, synthetic lethality, chromatin accessibility, kinetics, enhancer
Contact List
Stefan Kubicek
contact affiliationCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14 AKH BT 25.3 1090 Vienna, Austria
contact emailskubicek@cemm.oeaw.ac.at
lab head
Andre Mueller
contact affiliationResearch Center for Molecular Medicine of the Austrian Academy of Sciences
contact emailamueller@cemm.oeaw.ac.at
dataset submitter
Full Dataset Link List
Dataset FTP location
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