title: Multiple sequence-specific DNA-binding proteins mediate estrogen receptor signaling through a tethering pathway.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Heldring
authors.forename: Gary D
authors.initials: GD
authors.lastname: Isaacs
authors.forename: Adam G
authors.initials: AG
authors.lastname: Diehl
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Edwin
authors.initials: E
authors.lastname: Cheung
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Ranish
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D016133:Polymerase Chain Reaction; D040081:Protein Array Analysis; D040901:Proteomics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D016760:Proto-Oncogene Proteins c-fos; D018160:Receptors, Cytoplasmic and Nuclear; D018808:Transcription Factor AP-1