Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells

Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2748-53. doi: 10.1073/pnas.1018863108. Epub 2011 May 2.

Abstract

Estrogen receptor (ER) binds to distal enhancers within the genome and requires additional factors, such as the Forkhead protein FoxA1, for mediating chromatin interactions. We now show that the human Groucho protein, Transducin-like enhancer protein 1 (TLE1), positively assists some ER-chromatin interactions, a role that is distinct from its general role as a transcriptional repressor. We show that specific silencing of TLE1 inhibits the ability of ER to bind to a subset of ER binding sites within the genome, a phenomenon that results in perturbations in phospho-RNA Pol II recruitment. Furthermore, TLE1 is essential for effective ER-mediated cell division. We have discovered a distinct role for TLE1, as a necessary transcriptional component of the ER complex, where it facilitates ER-chromatin interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Chromatin / metabolism
  • Estrogen Receptor alpha / metabolism*
  • Estrogens / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Nuclear Factor 3-alpha / metabolism
  • Humans
  • Protein Binding / drug effects
  • Repressor Proteins / metabolism*
  • Transcription, Genetic* / drug effects

Substances

  • Chromatin
  • Estrogen Receptor alpha
  • Estrogens
  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Repressor Proteins
  • TLE1 protein, human
  • estrogen receptor alpha, human