EZH2 regulates the transcription of estrogen-responsive genes through association with REA, an estrogen receptor corepressor

Clara Hwang, Veda N. Giri, John C. Wilkinson, Casey Wright, Amanda S. Wilkinson, Kathleen A. Cooney, Colin S. Duckett

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase polycomb group (PcG) protein, which has been implicated in the process of cellular differentiation and cancer progression for both breast and prostate cancer. Although transcriptional repression by histone modification appears to contribute to the process of cellular differentiation, it is unclear what mediates the specificity of PcG proteins. Since EZH2 requires a binding partner for its histone methyltransferase activity, we surmised that evaluating interacting proteins might shed light on how the activity of EZH2 is regulated. Here we describe the identification of a novel binding partner of EZH2, the repressor of estrogen receptor activity (REA). REA functions as a transcriptional corepressor of the estrogen receptor and can potentiate the effect of anti-estrogens. REA expression levels have also previously been associated with the degree of differentiation of human breast cancers. We show here that EZH2 can also mediate the repression of estrogen-dependent transcription, and that moreover, the ability of both REA and EZH2 to repress estrogen-dependent transcription are mutually dependent. These data suggest that EZH2 may be recruited to specific target genes by its interaction with the estrogen receptor corepressor REA. The identification of a novel interaction between EZH2 and REA, two transcription factors that have been linked to breast cancer carcinogenesis, may lead to further insights into the process of deregulated gene expression in breast cancer.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalBreast Cancer Research and Treatment
Volume107
Issue number2
DOIs
StatePublished - Jan 2008
Externally publishedYes

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Keywords

  • Cancer
  • Estradiol
  • Estrogen receptor
  • Estrogen-dependent transcription
  • EZH2
  • REA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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