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Series GSE124903 Query DataSets for GSE124903
Status Public on Nov 21, 2019
Title mSWI/SNF functional genomic characterization of SMARCB1 mutants in SMARCB1-null and heterozygous settings
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Chromatin remodeling complexes regulate gene expression by shifting, evicting, and exchanging nucleosomes along the chromosomes of eukaryotic organisms. The mammalian SWI/SNF chromatin remodeling complex (mSWI/SNF or BAF) is mutated in over 20% of human cancers and loss of the SMARCB1 gene, encoding the BAF47 protein subunit, results in one of the most aggressive and lethal pediatric cancers. An accumulation of point mutations occurs at the C-terminal end of the protein, for which the functional ramifications are unknown. We previously demonstrated that reintroduction of SMARCB1 in SMARCB1-null malignant rhabdoid tumor cells results in a genome-wide increase of mSWI/SNF complex occupancy coupled with activation of PRC2-repressed genes. Here, we study the functional consequences that these point mutations exert on mSWI/SNF complex activity in SMARCB1-deficient tumor cells and extend this investigation to a CRISPR/Cas9-mediated SMARCB1-heterozygous mutant induced pluripotent stem cell. Intriguingly, we observe that the mutant complexes bind similarly to wild-type SMARCB1 complexes at enhancers throughout the genome but often fail to transcriptionally activate nearby genes in a cis-regulatory manner.
Overall design (1) ChIP-seq, ATAC-seq, MNase-seq and/or RNA-seq in human malignant rhaboid tumor cell lines (TTC1240 & G401) lentivirally infected with Empty vector or SMARCB1 constructs (FL, K34del, R377H, Y326*) and (2) ChIP-seq, RNA-seq, and ATAC-seq in human induced pluripotent stem cells (iPSCs) (WT control and SMARCB1 K364del heterozygous mutant)
Contributor(s) Valencia AM, Collings CK, Kadoch C
Citation(s) 31759698
Submission date Jan 10, 2019
Last update date Dec 04, 2019
Contact name Cigall Kadoch
Organization name Broad Institute of MIT and Harvard, Harvard Medical School, Dana-Farber Cancer Institute
Street address 450 Brookline Avenue
City Boston
State/province Massachusetts
ZIP/Postal code 02215
Country USA
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (102)
GSM3558535 SAH_iPSC_ATAC_SMARCB1_K364delHet_Day0_Rep1
GSM3558536 SAH_iPSC_ATAC_SMARCB1_K364delHet_Day0_Rep2
BioProject PRJNA514244
SRA SRP178151

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Supplementary file Size Download File type/resource
GSE124903_RAW.tar 18.3 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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