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Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1
Cheung E.1; Acevedo M.L.1; Cole P.A.5; Kraus W.L.1
2005-01-18
Source PublicationProceedings of the National Academy of Sciences of the United States of America
ISSN00278424
Volume102Issue:3Pages:559-564
Abstract

Estrogen signaling occurs through at least two distinct molecular pathways: (i) direct binding of liganded estrogen receptors (ERs) to estrogen-responsive DMA elements (EREs) (the "ER ERE pathway") and (ii) indirect recruitment of liganded ERs to activating protein-1 (AP-1)-responsive DMA elements via heterodimers of Fos and Jun (the "ER AP-1 pathway"). We have developed a biochemical assay for examining ligand-regulated transcription by ERs in the ER/AP-1 pathway. This assay recapitulates the altered (i.e., agonistic) pharmacology of selective estrogen receptor modulator drugs in this pathway reported previously by using various cell-based assays. We used our biochemical assay to examine the detailed mechanisms of ER/AP-1-dependent transcription. Our studies indicate that (i) ERα AP-1 complexes play a critical role in promoting the formation of stable RNA polymerase II preinitiation complexes leading to transcription initiation, (ii) chromatin is a key determinant of estrogen and selective estrogen receptor modulator signaling in the EIRα, AP-1 pathway, (iii) distinct domains of ERα are required for recruitment to DMA-bound Fos/Jun heterodimers and transcriptional activation at AP-1 sites, and (iv) different enhancer/activator combinations in the ERα and AP-1 pathways use coactivators in distinct ways. These studies have increased our understanding of the molecular mechanisms underlying ligand-dependent signaling in the ER/AP-1 pathway and demonstrate the usefulness of this biochemical approach.

KeywordChromatin Enhancer Fos/jun Heterodimers Histone Acetyltransferase Selective Estrogen Receptor Modulator
DOI10.1073/pnas.0407113102
URLView the original
Indexed BySCI
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000226436000009
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Cited Times [WOS]:41   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Cornell University
2.Weill Cornell Medical College
3.University of Puerto Rico
4.A-Star, Genome Institute of Singapore
5.The Johns Hopkins School of Medicine
Recommended Citation
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Cheung E.,Acevedo M.L.,Cole P.A.,et al. Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1[J]. Proceedings of the National Academy of Sciences of the United States of America,2005,102(3):559-564.
APA Cheung E.,Acevedo M.L.,Cole P.A.,&Kraus W.L..(2005).Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1.Proceedings of the National Academy of Sciences of the United States of America,102(3),559-564.
MLA Cheung E.,et al."Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1".Proceedings of the National Academy of Sciences of the United States of America 102.3(2005):559-564.
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