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Series GSE148175 Query DataSets for GSE148175
Status Public on Dec 22, 2020
Title Acute BAF perturbation causes immediate changes in chromatin accessibility
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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 diseases. Cells lacking the most frequently mutated subunits, like the ATPase SMARCA4, typically exhibit drastic chromatin accessibility changes, especially of important regulatory regions. 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 or activity of BAF complexes. Here, we utilize the dTAG system to induce acute degradation of BAF subunits in wildtype 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.
Overall design ATAC-seq, RNA-seq, PRO-seq experiments were performed in duplicates, ChIP-seq once. All experiments contain respective control samples.
ChIP antibody details: H3K27ac (Abcam, catalog# ab4729, lot# 3211741-1), ARID1A (Abcam, catalog# ab182560, lot# GR269670-9), IgG (Cell Signaling, catalog# CS 2729S, lot# 9), BRD4 (Abcam, catalog# ab128874, lot# GR3251918-7).
Contributor(s) Schick S, Grosche S, Kohl KE, Drpic D, Jaeger MG, Marella N, Schuster M, Rendeiro AF, Koren A, Petronczki M, Bock C, Mueller AC, Winter GE, Kubicek S
Citation(s) 33558760
Submission date Apr 06, 2020
Last update date Feb 25, 2021
Contact name Stefan Kubicek
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)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (209)
GSM4455503 HAP1 ARID2KO_SMARCA4dTAG_F5 dTAG 47 72h_1
GSM4455504 HAP1 ARID2KO_SMARCA4dTAG_F5 dTAG 47 24h_1
BioProject PRJNA623383
SRA SRP255443

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE148175_Pro-Seq-single-rep-raw-counts-BRM014-timecourse.txt.gz 965.2 Kb (ftp)(http) TXT
GSE148175_Pro-Seq-single-rep-raw-counts-WT-SMARCA4-dtag-dtag-timecourse.txt.gz 1.4 Mb (ftp)(http) TXT
GSE148175_Pro-Seq-single-rep-raw-counts-genebody-BRM014.txt.gz 2.1 Mb (ftp)(http) TXT
GSE148175_Pro-Seq-single-rep-raw-counts-genebody-SMARCA4KO-SMARCA2-dtag.txt.gz 1.3 Mb (ftp)(http) TXT
GSE148175_Pro-Seq-single-rep-raw-counts-genebody-WT-SMARCA4-dtag.txt.gz 1.7 Mb (ftp)(http) TXT
GSE148175_count_matrix_raw.txt.gz 8.3 Mb (ftp)(http) TXT
GSE148175_count_matrix_raw_atac_BRM014_ACBI1.csv.gz 2.0 Mb (ftp)(http) CSV
GSE148175_matrix_raw_72h_timepoint.csv.gz 2.9 Mb (ftp)(http) CSV
GSE148175_matrix_raw_timecourse.txt.gz 2.9 Mb (ftp)(http) TXT
GSE148175_rnaseq_deseq_ARID2KO_clone_counts_raw.tsv.gz 1.8 Mb (ftp)(http) TSV
GSE148175_rnaseq_deseq_BRG_clone_counts_raw.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE148175_rnaseq_deseq_CC1_clone_counts_raw.tsv.gz 1.9 Mb (ftp)(http) TSV
GSE148175_rnaseq_deseq_WT_clone_counts_raw.tsv.gz 1.9 Mb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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