Estrogen receptor (ER) beta or p53 attenuates ERalpha-mediated transcriptional activation on the BRCA2 promoter

J Biol Chem. 2008 Oct 31;283(44):29671-80. doi: 10.1074/jbc.M802785200. Epub 2008 Sep 2.

Abstract

BRCA2 is closely related to the pathogenesis of breast cancer. In the present study, we found that estrogen can activate BRCA2 transcription, which is estrogen receptor (ER) alpha-dependent. During estrogen treatment, ERalpha interacted with CREB-binding protein/p300, p68/p72, and MyoD and formed an activating transcriptional complex that could bind to many Sp1 sites on the BRCA2 promoter and activate its transcription by inducing histone acetylations. MyoD is a new component of ERalpha complex. ERbeta or p53 attenuated ERalpha-mediated transcriptional activation by preventing the recruitment of ERalpha transcriptional complex and histone acetylations on the BRCA2 promoter. ERbeta interacted with ERalpha and CREB-binding protein/p300 and formed a weak activating transcriptional complex that competed for binding to Sp1 sites with ERalpha transcriptional complex and slightly attenuated BRCA2 transcription. Different from ERbeta, p53 interacted with HDAC1 and CtBP1 and formed an inhibiting transcriptional complex that could compete for binding to Sp1 sites with ERalpha transcriptional complex and inhibit BRCA2 transcription more significantly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / metabolism
  • Apoptosis Regulatory Proteins
  • BRCA2 Protein / genetics*
  • Binding Sites
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / metabolism
  • Estrogen Receptor alpha / metabolism*
  • Estrogen Receptor beta / metabolism*
  • Gene Expression Regulation*
  • Histone Deacetylase 1
  • Histone Deacetylases / metabolism
  • Humans
  • Models, Genetic
  • Promoter Regions, Genetic
  • Sp1 Transcription Factor / chemistry
  • Transcriptional Activation*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • BLID protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • DNA-Binding Proteins
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Sp1 Transcription Factor
  • Tumor Suppressor Protein p53
  • Alcohol Oxidoreductases
  • C-terminal binding protein
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases