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Series GSE108386 Query DataSets for GSE108386
Status Public on Apr 30, 2019
Title Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities [ATAC-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
 
Overall design ATAC-seq samples for knockouts of BAF complex in the HAP1 cell line.
 
Contributor(s) Schick S, Rendeiro AF, Runggatscher K, Ringler A, Boidol B, Hinkel M, Májek P, Vulliard L, Penz T, Parapatics K, Schmidl C, Mensche J, Boehmelt G, Petronczki M, Mueller A, Bock C, Kubicek S
Citation(s) 31133746
Submission date Dec 21, 2017
Last update date Jul 30, 2019
Contact name Christoph Bock
E-mail(s) cbock@cemm.oeaw.ac.at
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (74)
GSM2897095 ATAC-seq_HAP1_ACTB_r1_2471_10
GSM2897096 ATAC-seq_HAP1_ACTB_r2_2471_10
GSM2897097 ATAC-seq_HAP1_ARID1A_r1_618_10
This SubSeries is part of SuperSeries:
GSE108390 Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities
Relations
BioProject PRJNA427145
SRA SRP127341

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Supplementary file Size Download File type/resource
GSE108386_baf_complex.atacseq-synth_lethal_peaks.raw_coverage.csv.gz 3.9 Mb (ftp)(http) CSV
GSE108386_baf_complex.atacseq.accessibility.annotated_metadata.csv.gz 40.4 Mb (ftp)(http) CSV
GSE108386_baf_complex.atacseq_peaks.raw_coverage.csv.gz 11.4 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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