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| Status |
Public on Nov 21, 2016 |
| Title |
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation [primary tissue_RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1.
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| |
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| Overall design |
RNA-seq for three primary Rhabdoid tumor samples
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| |
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| Contributor(s) |
Wang X, Lee RS, Alver BH, Park PJ, Roberts CW |
| Citation(s) |
27941797 |
| |
| Submission date |
Jul 29, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter J Park |
| E-mail(s) |
[email protected]
|
| Phone |
617-432-7373
|
| Organization name |
Harvard Medical School
|
| Department |
Center for Biomedical Informatics
|
| Street address |
10 Shattuck St
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE71506 |
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation |
|
| Relations |
| BioProject |
PRJNA291411 |
| SRA |
SRP061769 |
