The effects of estrogen-responsive element- and ligand-induced structural changes on the recruitment of cofactors and transcriptional responses by ER alpha and ER beta

Molecular Endocrinology
Ping YiM Muyan

Abstract

Estrogen signaling is mediated by ER alpha and -beta. ERs are converted from an inactive form to a transcriptionally active state through conformational changes induced by ligand and estrogen-responsive element (ERE) sequences. We show here that ER alpha and ER beta bind to an ERE independently from ER ligands. We found that although the binding affinity of ER beta for an ERE is 2-fold lower than that of ER alpha, both ERs use the same nucleotides for DNA contacts. We show that both EREs and ligands are independent modulators of ER conformation. Specifically, the ERE primarily determines the receptor-DNA affinity, whereas the structure of the ER ligand dictates the affinity of ER for particular cofactors. We found that the ligand-dependent cofactor transcriptional intermediary factor-2, through a distinct surface, also interacts with ER alpha preferentially and independently of ligand. The extent of interaction, however, is dependent upon the ER-ERE affinity. In transfected cells, ER alpha is more transcriptionally active than ER beta. The ERE sequence, however, determines the potency of gene induction when either ER subtype binds to an agonist. Antagonists prevent ERs from inducing transcription independently from ERE sequence...Continue Reading

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Citations

Mar 30, 2010·Molecular & Cellular Proteomics : MCP·Ivan NalvarteJan-Ake Gustafsson
May 8, 2004·Molecular and Cellular Endocrinology·Jing HuangMesut Muyan
Mar 24, 2004·Trends in Endocrinology and Metabolism : TEM·Christian J GruberJohannes C Huber
Apr 12, 2008·The Journal of Steroid Biochemistry and Molecular Biology·Xiaodong LiMesut Muyan
Jan 1, 2009·International Journal of Cancer. Journal International Du Cancer·Sudipan KarmakarCarolyn L Smith
Aug 18, 2006·Molecular Aspects of Medicine·Paolo AscenziMaria Marino
Sep 23, 2008·Biochimica Et Biophysica Acta·Marinella ZilliUNKNOWN Consorzio Interuniversitario Nazionale per la Bio-Oncologia (CINBO)
Feb 4, 2016·Scientific Reports·Chunyu WangXiongwei Zhu
Feb 22, 2007·The Journal of Clinical Endocrinology and Metabolism·Ryan MartinHugh S Taylor
Feb 11, 2004·Endocrine Reviews·Carolyn L Smith, Bert W O'Malley
Jun 11, 2019·Frontiers in Endocrinology·Aradhana RaniJohn Murphy

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