Multiple sequence-specific DNA-binding proteins mediate estrogen receptor signaling through a tethering pathway

Mol Endocrinol. 2011 Apr;25(4):564-74. doi: 10.1210/me.2010-0425. Epub 2011 Feb 17.


The indirect recruitment (tethering) of estrogen receptors (ERs) to DNA through other DNA-bound transcription factors (e.g. activator protein 1) is an important component of estrogen-signaling pathways, but our understanding of the mechanisms of ligand-dependent activation in this pathway is limited. Using proteomic, genomic, and gene-specific analyses, we demonstrate that a large repertoire of DNA-binding transcription factors contribute to estrogen signaling through the tethering pathway. In addition, we define a set of endogenous genes for which ERα tethering through activator protein 1 (e.g. c-Fos) and cAMP response element-binding protein family members mediates estrogen responsiveness. Finally, we show that functional interplay between c-Fos and cAMP response element-binding protein 1 contributes to estrogen-dependent regulation through the tethering pathway. Based on our results, we conclude that ERα recruitment in the tethering pathway is dependent on the ligand-induced formation of transcription factor complexes that involves interplay between the transcription factors from different protein families.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Mass Spectrometry
  • Polymerase Chain Reaction
  • Protein Array Analysis
  • Proteomics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction*
  • Transcription Factor AP-1 / metabolism


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Proto-Oncogene Proteins c-fos
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factor AP-1