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Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

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

Kimberly M Baker1, Guo Wei, Alicia Erbe Schaffner

  • 1Department of Molecular Genetics and The Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA.

The Journal of Biological Chemistry
|March 15, 2003
PubMed

Insights

Ets-2 (Ets-2) functions not only as a transcriptional activator but also as a repressor. It interacts with the SWI/SNF complex to repress BRCA1 gene expression, particularly in breast cancer cells.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cancer Biology

Background:

  • Ets-2 is known as a transcriptional activator, modulated by ras-dependent phosphorylation.
  • Emerging evidence suggests Ets-2 may also function as a transcriptional repressor.

Purpose of the Study:

  • To investigate the repressive role of Ets-2.
  • To elucidate the mechanism by which Ets-2 represses gene activity.
  • To identify co-factors involved in Ets-2-mediated repression.

Main Methods:

  • Utilized MCF-7 breast cancer cells.
  • Employed a BRCA1 promoter-luciferase reporter assay.
  • Performed co-immunoprecipitation and in vitro interaction assays.
  • Investigated protein interactions with the Ets-2 pointed domain.

Main Results:

  • Exogenous Ets-2 repressed BRCA1 promoter activity in MCF-7 cells.
  • Overproduction of Ets-2 decreased endogenous BRCA1 mRNA levels.
  • Identified interactions between Ets-2 and components of the mammalian SWI/SNF chromatin remodeling complex, including Brg-1, BAF57/p50, and Ini1.
  • Demonstrated phosphorylation-dependent interaction between Ets-2 pointed domain and Brg-1.
  • Showed that co-expression of Brg-1 and Ets-2 repressed the BRCA1 promoter reporter.

Conclusions:

  • Ets-2 can function as a transcriptional repressor.
  • Mammalian SWI/SNF complex components are required as co-repressors for Ets-2.
  • This interaction plays a role in regulating BRCA1 gene expression, with implications for breast cancer.

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