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| Status |
Public on Aug 02, 2018 |
| Title |
Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis. [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Chromosomal rearrangements resulting in the fusion of TMRPSS2, an androgen-regulated gene, and the ETS family transcription factor ERG occur in over half of prostate cancers. However, the mechanism by which ERG promotes oncogenic gene expression and proliferation remains incompletely understood. Here, we identify a binding interaction between ERG and the mammalian SWI/SNF (BAF) ATP-dependent chromatin remodeling complex, which is conserved among other ETS factors, including ETV1, ETV4, and ETV5. We find that ERG drives genome-wide retargeting of BAF complexes in a manner dependent on binding of ERG to the ETS DNA motif. Moreover, ERG requires intact BAF complexes for chromatin occupancy and BAF complex ATPase activity for target gene regulation. In a prostate organoid model, BAF complexes are required for ERG-mediated basal-to-luminal transition, a hallmark of ERG activity in prostate cancer. These observations suggest a fundamental interdependence between ETS transcription factors and BAF chromatin remodeling complexes in cancer.
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| Overall design |
Prostate cancer cell lines (VCaP, LNCaP) and adrenacorticoid carcinoma cell lines (SW13) were lentivirally infected with respective expression/knockdown constructs, selected, and harvested for RNA-seq.
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| Contributor(s) |
Pulice J, Kadoch C |
| Citation(s) |
30078722 |
| |
| Submission date |
Feb 15, 2018 |
| Last update date |
Mar 26, 2019 |
| 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 (24)
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| This SubSeries is part of SuperSeries: |
| GSE110657 |
Binding of TMPRSS2-ERG to BAF Chromatin Remodeling Complexes Mediates Prostate Oncogenesis. |
|
| Relations |
| BioProject |
PRJNA434202 |
| SRA |
SRP132915 |
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