Nucleic Acids Research, 2001, Vol. 29, No. 14 2905-2919
© 2001 Oxford University Press
Estrogen receptor interaction with estrogen response elements
Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
The estrogen receptor (ER) is a ligand-activated enhancer protein that is a member of the steroid/nuclear receptor superfamily. Two genes encode mammalian ER: ER
and ERß. ER binds to specific DNA sequences called estrogen response elements (EREs) with high affinity and transactivates gene expression in response to estradiol (E2). The purpose of this review is to summarize how natural and synthetic variations in the ERE sequence impact the affinity of ER–ERE binding and E2-induced transcriptional activity. Surprisingly, although the consensus ERE sequence was delineated in 1989, there are only seven natural EREs for which both ER binding affinity and transcriptional activation have been examined. Even less information is available regarding how variations in ERE sequence impact ERß binding and transcriptional activity. Review of data from our own laboratory and those in the literature indicate that ER binding affinity does not relate linearly with E2-induced transcriptional activation. We suggest that the reasons for this discord include cellular amounts of coactivators and adaptor proteins that play roles both in ER binding and transcriptional activation; phosphorylation of ER and other proteins involved in transcriptional activation; and sequence-specific and protein-induced alterations in chromatin architecture.
* Tel: +1 502 852 3668; Fax: +1 502 852 6222; Email: carolyn.klinge{at}louisville.edu
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S. Tang, S. L. Tan, S. K. Ramadoss, A. P. Kumar, M.-H. E. Tang, and V. B. Bajic Computational method for discovery of estrogen responsive genes Nucleic Acids Res., December 1, 2004; 32(21): 6212 - 6217. [Abstract] [Full Text] [PDF]
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J. Ashby and J. Odum Gene Expression Changes in the Immature Rat Uterus: Effects of Uterotrophic and Sub-Uterotrophic Doses of Bisphenol A Toxicol. Sci., December 1, 2004; 82(2): 458 - 467. [Abstract] [Full Text] [PDF]
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D. Das, R. C. Peterson, and W. M. Scovell High Mobility Group B Proteins Facilitate Strong Estrogen Receptor Binding to Classical and Half-Site Estrogen Response Elements and Relax Binding Selectivity Mol. Endocrinol., November 1, 2004; 18(11): 2616 - 2632. [Abstract] [Full Text] [PDF]
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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]
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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]
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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]
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W. Shao, E. K. Keeton, D. P. McDonnell, and M. Brown Coactivator AIB1 links estrogen receptor transcriptional activity and stability PNAS, August 10, 2004; 101(32): 11599 - 11604. [Abstract] [Full Text] [PDF]
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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]
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 V. T. Gaddy, J. T. Barrett, J. N. Delk, A. M. Kallab, A. G. Porter, and P. V. Schoenlein Mifepristone Induces Growth Arrest, Caspase Activation, and Apoptosis of Estrogen Receptor-Expressing, Antiestrogen-Resistant Breast Cancer Cells Clin. Cancer Res., August 1, 2004; 10(15): 5215 - 5225. [Abstract] [Full Text] [PDF]
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S. K. Mishra, A. H. Talukder, A. E. Gururaj, Z. Yang, R. R. Singh, M. G. Mahoney, C. Franci, R. K. Vadlamudi, and R. Kumar Upstream Determinants of Estrogen Receptor-{alpha} Regulation of Metastatic Tumor Antigen 3 Pathway J. Biol. Chem., July 30, 2004; 279(31): 32709 - 32715. [Abstract] [Full Text] [PDF]
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S. O. Mueller, S. Simon, K. Chae, M. Metzler, and K. S. Korach Phytoestrogens and Their Human Metabolites Show Distinct Agonistic and Antagonistic Properties on Estrogen Receptor {alpha} (ER{alpha}) and ER{beta} in Human Cells Toxicol. Sci., July 1, 2004; 80(1): 14 - 25. [Abstract] [Full Text] [PDF]
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F. Stossi, D. H. Barnett, J. Frasor, B. Komm, C. R. Lyttle, and B. S. Katzenellenbogen Transcriptional Profiling of Estrogen-Regulated Gene Expression via Estrogen Receptor (ER) {alpha} or ER{beta} in Human Osteosarcoma Cells: Distinct and Common Target Genes for These Receptors Endocrinology, July 1, 2004; 145(7): 3473 - 3486. [Abstract] [Full Text] [PDF]
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O. Kretz, L. Fester, U. Wehrenberg, L. Zhou, S. Brauckmann, S. Zhao, J. Prange-Kiel, T. Naumann, H. Jarry, M. Frotscher, et al. Hippocampal Synapses Depend on Hippocampal Estrogen Synthesis J. Neurosci., June 30, 2004; 24(26): 5913 - 5921. [Abstract] [Full Text] [PDF]
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V. Bourdeau, J. Deschenes, R. Metivier, Y. Nagai, D. Nguyen, N. Bretschneider, F. Gannon, J. H. White, and S. Mader Genome-Wide Identification of High-Affinity Estrogen Response Elements in Human and Mouse Mol. Endocrinol., June 1, 2004; 18(6): 1411 - 1427. [Abstract] [Full Text] [PDF]
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H.-W. Tsai, J. A. Katzenellenbogen, B. S. Katzenellenbogen, and M. A. Shupnik Protein Kinase A Activation of Estrogen Receptor {alpha} Transcription Does Not Require Proteasome Activity and Protects the Receptor from Ligand-Mediated Degradation Endocrinology, June 1, 2004; 145(6): 2730 - 2738. [Abstract] [Full Text] [PDF]
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P. L. R. Ee, S. Kamalakaran, D. Tonetti, X. He, D. D. Ross, and W. T. Beck Identification of a Novel Estrogen Response Element in the Breast Cancer Resistance Protein (ABCG2) Gene Cancer Res., February 15, 2004; 64(4): 1247 - 1251. [Abstract] [Full Text] [PDF]
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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]
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 J-C Lambert, N Coyle, and C Lendon The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease J. Med. Genet., February 1, 2004; 41(2): 104 - 112. [Abstract] [Full Text] [PDF]
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 J. M. Naciff and G. P. Daston Toxicogenomic Approach to Endocrine Disrupters: Identification of a Transcript Profile Characteristic of Chemicals with Estrogenic Activity Toxicol Pathol, February 1, 2004; 32(2_suppl): 59 - 70. [Abstract] [PDF]
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M. C. Frith, U. Hansen, J. L. Spouge, and Z. Weng Finding functional sequence elements by multiple local alignment Nucleic Acids Res., January 2, 2004; 32(1): 189 - 200. [Abstract] [Full Text] [PDF]
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T. L. Ramsey, K. E. Risinger, S. C. Jernigan, K. A. Mattingly, and C. M. Klinge Estrogen Receptor {beta} Isoforms Exhibit Differences in Ligand-Activated Transcriptional Activity in an Estrogen Response Element Sequence-Dependent Manner Endocrinology, January 1, 2004; 145(1): 149 - 160. [Abstract] [Full Text] [PDF]
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A. M. Davis, M. L. Seney, H. J. Walker, and S. A. Tobet Differential Colocalization of Islet-1 and Estrogen Receptor {alpha} in the Murine Preoptic Area and Hypothalamus during Development Endocrinology, January 1, 2004; 145(1): 360 - 366. [Abstract] [Full Text] [PDF]
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K. R. Coser, J. Chesnes, J. Hur, S. Ray, K. J. Isselbacher, and T. Shioda Global analysis of ligand sensitivity of estrogen inducible and suppressible genes in MCF7/BUS breast cancer cells by DNA microarray PNAS, November 25, 2003; 100(24): 13994 - 13999. [Abstract] [Full Text] [PDF]
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X.-H. Li and D. E. Ong Cellular Retinoic Acid-binding Protein II Gene Expression Is Directly Induced by Estrogen, but Not Retinoic Acid, in Rat Uterus J. Biol. Chem., September 12, 2003; 278(37): 35819 - 35825. [Abstract] [Full Text] [PDF]
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 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]
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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]
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K. M. M. Kelley, B. G. Rowan, and M. Ratnam Modulation of the Folate Receptor {alpha} Gene by the Estrogen Receptor: Mechanism and Implications in Tumor Targeting Cancer Res., June 1, 2003; 63(11): 2820 - 2828. [Abstract] [Full Text] [PDF]
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L. H. Wang, X. Y. Yang, X. Zhang, K. Mihalic, W. Xiao, and W. L. Farrar The cis Decoy against the Estrogen Response Element Suppresses Breast Cancer Cells via Target Disrupting c-fos not Mitogen-activated Protein Kinase Activity Cancer Res., May 1, 2003; 63(9): 2046 - 2051. [Abstract] [Full Text] [PDF]
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J. M. Naciff, G. J. Overmann, S. M. Torontali, G. J. Carr, J. P. Tiesman, B. D. Richardson, and G. P. Daston Gene Expression Profile Induced by 17{alpha}-Ethynyl Estradiol in the Prepubertal Female Reproductive System of the Rat Toxicol. Sci., April 1, 2003; 72(2): 314 - 330. [Abstract] [Full Text] [PDF]
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J. V. Ponomarenko, T. I. Merkulova, G. V. Orlova, O. N. Fokin, E. V. Gorshkova, A. S. Frolov, V. P. Valuev, and M. P. Ponomarenko rSNP_Guide, a database system for analysis of transcription factor binding to DNA with variations: application to genome annotation Nucleic Acids Res., January 1, 2003; 31(1): 118 - 121. [Abstract] [Full Text] [PDF]
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