Multiple Sequence-Specific DNA-Binding Proteins Mediate Estrogen Receptor Signaling through a Tethering Pathway

TitleMultiple Sequence-Specific DNA-Binding Proteins Mediate Estrogen Receptor Signaling through a Tethering Pathway
Publication TypeJournal Article
Year of Publication2011
AuthorsHeldring N, Isaacs GD, Diehl AG, Sun M, Cheung E, Ranish J, Kraus WL
JournalMol Endocrinol
Date PublishedFeb 17
PMID21330404
AbstractThe 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 ERalpha 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 ERalpha 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.

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