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Series GSE90631 Query DataSets for GSE90631
Status Public on Sep 25, 2017
Title SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters [ChIP-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary BAF complex perturbations contribute to over 20% of human cancer, yet the mechanisms by which these alterations drive oncogenesis remain poorly understood. The driving role for BAF complex mutations in cancer was first documented in malignant rhabdoid tumor (MRT), an aggressive pediatric cancer in which loss of SMARCB1 (also known as BAF47, INI1, hSNF5), a core BAF complex subunit, is the hallmark genetic alteration. We find that loss of BAF47 destabilizes the biochemical affinity of BAF complexes on chromatin without significantly impairing complex integrity or subunit composition. Rescue of BAF47 in BAF47-deficient sarcoma cell lines results in global increases in BAF complex occupancy, which mediates a major gain in enhancer activation. In addition, we find BAF47 targets BAF complexes to bivalent promoters, resolving bivalency to activation through opposition of polycomb-mediated repression. These findings demonstrate collaborative gene activation by the BAF complex through distinct mechanisms, highlighting specific BAF complex functions that are coopted or abated to drive human cancers and developmental disorders.
 
Overall design Malignant rhabdoid tumor (G401, TTC1240) or epithelioid sarcoma (HS-ES-2M, VA-ES-BJ) cell lines were lentivirally infected with either an empty vector control or a constitutive vector expressing BAF47, selected for 48 hours with blasticidin, then grown for 5 days, at which point cells were harvested for ChIP-seq preparation.
 
Contributor(s) Pulice J, Kadoch C
Citation(s) 28945250
BioProject PRJNA352986
Submission date Nov 29, 2016
Last update date Jul 25, 2021
Contact name Cigall Kadoch
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Lab Kadoch Lab
Street address 450 Brookline Avenue
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (62)
GSM2409659 G401_empty_BAF155
GSM2409660 G401_empty_H3K27ac
GSM2409661 G401_empty_H3K27me3
This SubSeries is part of SuperSeries:
GSE90634 SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters

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Supplementary file Size Download File type/resource
GSE90631_MRT_ChIP_Antibodies.xlsx 47.5 Kb (ftp)(http) XLSX
GSE90631_RAW.tar 63.0 Mb (http)(custom) TAR (of BROADPEAK, NARROWPEAK)
SRA Run SelectorHelp
Raw data provided as supplementary file
Processed data provided as supplementary file

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