Ets-2 and components of mammalian SWI/SNF form a repressor complex that negatively regulates the BRCA1 promoter

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Abstract

Ets-2 is a transcriptional activator that can be modulated by ras-dependent phosphorylation. Evidence is presented indicating that ets-2 can also act as a transcriptional repressor. In the breast cancer cell line MCF-7, exogenous ets-2 repressed the activity of a BRCA1 promoter-luciferase reporter dependent on a conserved ets-2-binding site in this promoter. Conditional overproduction of ets-2 in MCF-7 cells resulted in repression of endogenous BRCA1 mRNA expression. To address the mechanism by which ets-2 could act as a repressor, a biochemical approach was used to identify proteins that interacted with the ets-2 pointed domain. From this analysis, components of the mammalian SWI/ SNF chromatin remodeling complex were found to interact with ets-2. Brg-1, the ATP-hydrolyzing component of the SWI/SNF complex, along with the BAF57/p50 and Inil subunits could be co-immunoprecipitated from cells with ets-2. The pointed domain of ets-2 directly interacted in vitro with the C-terminal region of Brg-1 in a phosphorylation-dependent manner. The combination of Brg-1 and ets-2 could repress the BRCA1 promoter reporter in transfection assays. These results support a role for ets-2 as a repressor and indicate that components of the mammalian SNF/SWI complex are required as co-repressors.

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Baker, K. M., Wei, G., Schaffner, A. E., & Ostrowski, M. C. (2003). Ets-2 and components of mammalian SWI/SNF form a repressor complex that negatively regulates the BRCA1 promoter. Journal of Biological Chemistry, 278(20), 17876–17884. https://doi.org/10.1074/jbc.M209480200

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