This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yi, P. Articles by Muyan, M. Search for Related Content PubMed PubMed Citation Articles by Yi, P. Articles by Muyan, M.

The Effects of Estrogen-Responsive Element- and Ligand-Induced Structural Changes on the Recruitment of Cofactors and Transcriptional Responses by ER and ERß

Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642

Address all correspondence and requests for reprints to: Dr. Mesut Muyan, Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 712, Rochester, New York 14642. E-mail: Mesut_Muyan{at}urmc.rochester.edu.

Estrogen signaling is mediated by ER and -ß. 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 and ERß bind to an ERE independently from ER ligands. We found that although the binding affinity of ERß for an ERE is 2-fold lower than that of ER, 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 preferentially and independently of ligand. The extent of interaction, however, is dependent upon the ER-ERE affinity. In transfected cells, ER is more transcriptionally active than ERß. 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 sequences. Thus, ERE- and ligand-induced structural changes are independent determinants for the recruitment of cofactors and transcriptional responses. The ability of ER to differentially recruit a cofactor could contribute to ER subtype-specific gene responses.

This article has been cited by other articles:

				H. A. Molenda-Figueira, S. D. Murphy, K. L. Shea, N. K. Siegal, Y. Zhao, J. G. Chadwick Jr., L. A. Denner, and M. J. Tetel Steroid Receptor Coactivator-1 from Brain Physically Interacts Differentially with Steroid Receptor Subtypes Endocrinology, October 1, 2008; 149(10): 5272 - 5279. [Abstract] [Full Text] [PDF]

				X. Li, S. L Nott, Y. Huang, R. Hilf, R. A Bambara, X. Qiu, A. Yakovlev, S. Welle, and M. Muyan Gene expression profiling reveals that the regulation of estrogen-responsive element-independent genes by 17{beta}-estradiol-estrogen receptor {beta} is uncoupled from the induction of phenotypic changes in cell models J. Mol. Endocrinol., May 1, 2008; 40(5): 211 - 229. [Abstract] [Full Text] [PDF]

				W. Y. X. Peh, E. Reimhult, H. F. Teh, J. S. Thomsen, and X. Su Understanding Ligand Binding Effects on the Conformation of Estrogen Receptor {alpha}-DNA Complexes: A Combinational Quartz Crystal Microbalance with Dissipation and Surface Plasmon Resonance Study Biophys. J., June 15, 2007; 92(12): 4415 - 4423. [Abstract] [Full Text] [PDF]

				R. Martin, M. B. Taylor, G. Krikun, C. Lockwood, G. E. Akbas, and H. S. Taylor Differential Cell-Specific Modulation of HOXA10 by Estrogen and Specificity Protein 1 Response Elements J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1920 - 1926. [Abstract] [Full Text] [PDF]

				M. E. Dickson, M. B. Zimmerman, K. Rahmouni, and C. D. Sigmund The -20 and -217 Promoter Variants Dominate Differential Angiotensinogen Haplotype Regulation in Angiotensinogen-Expressing Cells Hypertension, March 1, 2007; 49(3): 631 - 639. [Abstract] [Full Text] [PDF]

				J. R. Schultz-Norton, W. H. McDonald, J. R. Yates, and A. M. Nardulli Protein Disulfide Isomerase Serves as a Molecular Chaperone to Maintain Estrogen Receptor {alpha} Structure and Function Mol. Endocrinol., September 1, 2006; 20(9): 1982 - 1995. [Abstract] [Full Text] [PDF]

				J. Huang, X. Li, C. A. Maguire, R. Hilf, R. A. Bambara, and M. Muyan Binding of Estrogen Receptor {beta} to Estrogen Response Element in Situ Is Independent of Estradiol and Impaired by Its Amino Terminus Mol. Endocrinol., November 1, 2005; 19(11): 2696 - 2712. [Abstract] [Full Text] [PDF]

				S K Nair, T J Thomas, N J Greenfield, A Chen, H He, and T Thomas Conformational dynamics of estrogen receptors {alpha} and {beta} as revealed by intrinsic tryptophan fluorescence and circular dichroism J. Mol. Endocrinol., October 1, 2005; 35(2): 211 - 223. [Abstract] [Full Text] [PDF]

				A. van de Stolpe, A. J. Slycke, M. O. Reinders, A. W. M. Zomer, S. Goodenough, C. Behl, A. F. Seasholtz, and P. T. van der Saag Estrogen Receptor (ER)-Mediated Transcriptional Regulation of the Human Corticotropin-Releasing Hormone-Binding Protein Promoter: Differential Effects of ER{alpha} and ER{beta} Mol. Endocrinol., December 1, 2004; 18(12): 2908 - 2923. [Abstract] [Full Text] [PDF]

				G. M. Leong, S. Moverare, J. Brce, N. Doyle, K. Sjogren, K. Dahlman-Wright, J.-A. Gustafsson, K. K. Y. Ho, C. Ohlsson, and K.-C. Leung Estrogen Up-Regulates Hepatic Expression of Suppressors of Cytokine Signaling-2 and -3 in Vivo and in Vitro Endocrinology, December 1, 2004; 145(12): 5525 - 5531. [Abstract] [Full Text] [PDF]

				K. Stokes, B. Alston-Mills, and C. Teng Estrogen response element and the promoter context of the human and mouse lactoferrin genes influence estrogen receptor {alpha}-mediated transactivation activity in mammary gland cells J. Mol. Endocrinol., October 1, 2004; 33(2): 315 - 334. [Abstract] [Full Text] [PDF]

				C M Klinge, S C Jernigan, K A Mattingly, K E Risinger, and J Zhang Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors {alpha} and {beta} by coactivators and corepressors J. Mol. Endocrinol., October 1, 2004; 33(2): 387 - 410. [Abstract] [Full Text] [PDF]

				X. Li, J. Huang, P. Yi, R. A. Bambara, R. Hilf, and M. Muyan Single-Chain Estrogen Receptors (ERs) Reveal that the ER{alpha}/{beta} Heterodimer Emulates Functions of the ER{alpha} Dimer in Genomic Estrogen Signaling Pathways Mol. Cell. Biol., September 1, 2004; 24(17): 7681 - 7694. [Abstract] [Full Text] [PDF]

				R. O'Lone, M. C. Frith, E. K. Karlsson, and U. Hansen Genomic Targets of Nuclear Estrogen Receptors Mol. Endocrinol., August 1, 2004; 18(8): 1859 - 1875. [Abstract] [Full Text] [PDF]

				F. Barchiesi, E. K. Jackson, B. Imthurn, J. Fingerle, D. G. Gillespie, and R. K. Dubey Differential Regulation of Estrogen Receptor Subtypes {alpha} and {beta} in Human Aortic Smooth Muscle Cells by Oligonucleotides and Estradiol J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2373 - 2381. [Abstract] [Full Text] [PDF]

				C. L. Smith and B. W. O'Malley Coregulator Function: A Key to Understanding Tissue Specificity of Selective Receptor Modulators Endocr. Rev., February 1, 2004; 25(1): 45 - 71. [Abstract] [Full Text] [PDF]

				J. Matthews and J.-A. Gustafsson Estrogen Signaling: A Subtle Balance Between ER{alpha} and ER{beta} Mol. Interv., August 1, 2003; 3(5): 281 - 292. [Abstract] [Full Text] [PDF]

				V. B. Bajic, S. L. Tan, A. Chong, S. Tang, A. Strom, J.-A. Gustafsson, C.-Y. Lin, and E. T. Liu Dragon ERE Finder version 2: a tool for accurate detection and analysis of estrogen response elements in vertebrate genomes Nucleic Acids Res., July 1, 2003; 31(13): 3605 - 3607. [Abstract] [Full Text] [PDF]

				X. Li, J. Wong, S. Y. Tsai, M.-J. Tsai, and B. W. O'Malley Progesterone and Glucocorticoid Receptors Recruit Distinct Coactivator Complexes and Promote Distinct Patterns of Local Chromatin Modification Mol. Cell. Biol., June 1, 2003; 23(11): 3763 - 3773. [Abstract] [Full Text] [PDF]

				P. Yi, S. Bhagat, R. Hilf, R. A. Bambara, and M. Muyan Differences in the Abilities of Estrogen Receptors to Integrate Activation Functions Are Critical for Subtype-Specific Transcriptional Responses Mol. Endocrinol., August 1, 2002; 16(8): 1810 - 1827. [Abstract] [Full Text] [PDF]