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| Status |
Public on Sep 25, 2017 |
| Title |
SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters [Hi-C] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| 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.
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| Overall design |
VA-ES-BJ epithelioid sarcoma 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 chromatin capture followed by sequencing (Hi-C).
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| Contributor(s) |
Pulice J, Kadoch C |
| Citation(s) |
28945250 |
| BioProject |
PRJNA352986 |
| |
| Submission date |
Nov 29, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Cigall Kadoch |
| Organization name |
Dana-Farber Cancer Institute
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| Department |
Pediatric Oncology
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| Lab |
Kadoch Lab
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| Street address |
450 Brookline Avenue
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (4)
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| 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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