AI Article Synopsis
- Over half of prostate cancers involve chromosomal rearrangements that fuse the TMPRSS2 gene and the ERG transcription factor, but the exact role of ERG in cancer progression is not fully understood.
- Researchers discovered that ERG interacts with the BAF chromatin remodeling complex, influencing how genes are expressed and how cells proliferate.
- In prostate organoids, the presence of BAF complexes is crucial for enabling ERG to facilitate a specific cell transition related to cancer, indicating a vital relationship between ETS factors and BAF complexes in cancer biology.
Article Abstract
Chromosomal rearrangements resulting in the fusion of TMPRSS2, 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 oncogenic 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140332 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2018.06.040 | DOI Listing |
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