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

Nina Heldring, Gary D. Isaacs, Adam G. Diehl, Miao Sun, Edwin Cheung, Jeffrey A. Ranish, W. Lee Kraus

Research output: Contribution to journalArticle

36 Scopus citations


The indirect recruitment (tethering) of estrogen receptors (ERs) to DNA through other DNAbound transcription factors (e.g. activator protein 1) is an important component of estrogensignaling 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 ER_ tethering through activator protein 1 (e.g. c-Fos) and cAMP response elementbinding 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 ER_ 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.

Original languageEnglish (US)
Pages (from-to)564-574
Number of pages11
JournalMolecular Endocrinology
Issue number4
StatePublished - Apr 1 2011


ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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