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Steroid Hormone Receptors: Interaction with Deoxyribonucleic Acid and Transcription Factors^*

Institut für Molekularbiologie und Tumorforschung, Philipps-Universtät Marburg D-35037 Marburg, Germany

Correspondence: Address requests for reprints to: M. Beato, M.D., Institut für Molekularbiologie und Tumorforschung, Emil-Mannkopff-Str. 2, D-35037 Marburg, Germany.

Abstract

GENE regulation by steroid hormones is mediated by binding of the hormone ligand to the corresponding receptor that triggers a complex set of interactions of the hormone receptors with each other, with DNA in chromatin, and with a variety of other proteins. In this review we attempt to summarize what is known about these interactions using as the main example the regulation of mouse mammary tumor virus transcription by glucocorticoids and progestins. We describe in some detail the interaction of monomers and homodimers of the steroid receptors with their recognition sequences, and the molecular mechanism used to discriminate between the responsive elements for glucocorticoids/progestins and estrogens. We then review the interactions between homologous and heterologous hormone receptors on complex hormone regulatory regions, before devoting some attention to the synergistic and inhibitory interactions of hormone receptors with other transcription factors. Finally we briefly summarize some of the possible mechanisms that modulate the molecular interactions of hormone receptors. In addition to ligand binding, these include receptor phosphorylation, changes in DNA topology, and the organization of DNA in nucleosomes. From this overview we draw the tentative conclusion that the specificity of the hormonal response in different cells results from a combination of developmental restrictions both in the accessibility of genomic sequence and in the repertoire of regulatory proteins present in each particular cell. In addition, the array of regulatory sequences in DNA and chromatin determines the precise nature of the macromolecular interactions of the receptors that are modulated by their degree of phosphorylation.

Footnotes

^* The experimental work reported in this paper has been supported by grants from the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.

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				M. S. Ricci, D. G. Toscano, C. J. Mattingly, and W. A. Toscano Jr. Estrogen Receptor Reduces CYP1A1 Induction in Cultured Human Endometrial Cells J. Biol. Chem., February 5, 1999; 274(6): 3430 - 3438. [Abstract] [Full Text] [PDF]

				D. Chen, P. E. Pace, R. C. Coombes, and S. Ali Phosphorylation of Human Estrogen Receptor alpha  by Protein Kinase A Regulates Dimerization Mol. Cell. Biol., February 1, 1999; 19(2): 1002 - 1015. [Abstract] [Full Text] [PDF]

				T. Murata and M. Yamaguchi Promoter Characterization of the Rat Gene for Ca2+-binding Protein Regucalcin. TRANSCRIPTIONAL REGULATION BY SIGNALING FACTORS J. Biol. Chem., January 15, 1999; 274(3): 1277 - 1285. [Abstract] [Full Text] [PDF]

				O. Eickelberg, M. Roth, R. Lorx, V. Bruce, J. Rudiger, M. Johnson, and L.-H. Block Ligand-independent Activation of the Glucocorticoid Receptor by beta 2-Adrenergic Receptor Agonists in Primary Human Lung Fibroblasts and Vascular Smooth Muscle Cells J. Biol. Chem., January 8, 1999; 274(2): 1005 - 1010. [Abstract] [Full Text] [PDF]

				W. Xie, R. Duan, and S. Safe Estrogen Induces Adenosine Deaminase Gene Expression in MCF-7 Human Breast Cancer Cells: Role of Estrogen Receptor-Sp1 Interactions Endocrinology, January 1, 1999; 140(1): 219 - 227. [Abstract] [Full Text]

				R. A. Ramos, W. J. Meilandt, E. C. Wang, and G. L. Firestone Dysfunctional glucocorticoid receptor with a single point mutation ablates the CCAAT/enhancer binding protein-dependent growth suppression response in a steroid-resistant rat hepatoma cell variant FASEB J, January 1, 1999; 13(1): 169 - 180. [Abstract] [Full Text]

				H. M. Zhou and W. W. Walthall UNC-55, an Orphan Nuclear Hormone Receptor, Orchestrates Synaptic Specificity among Two Classes of Motor Neurons in Caenorhabditis elegans J. Neurosci., December 15, 1998; 18(24): 10438 - 10444. [Abstract] [Full Text] [PDF]

				S. A. Leonhardt, M. Altmann, and D. P. Edwards Agonist and Antagonists Induce Homodimerization and Mixed Ligand Heterodimerization of Human Progesterone Receptors in Vivo by a Mammalian Two-Hybrid Assay Mol. Endocrinol., December 1, 1998; 12(12): 1914 - 1930. [Abstract] [Full Text]

				V. M. Christoffels, T. Grange, K. H. Kaestner, T. J. Cole, G. J. Darlington, C. M. Croniger, and W. H. Lamers Glucocorticoid Receptor, C/EBP, HNF3, and Protein Kinase A Coordinately Activate the Glucocorticoid Response Unit of the Carbamoylphosphate Synthetase I Gene Mol. Cell. Biol., November 1, 1998; 18(11): 6305 - 6315. [Abstract] [Full Text]

				V. Boonyaratanakornkit, V. Melvin, P. Prendergast, M. Altmann, L. Ronfani, M. E. Bianchi, L. Taraseviciene, S. K. Nordeen, E. A. Allegretto, and D. P. Edwards High-Mobility Group Chromatin Proteins 1 and 2 Functionally Interact with Steroid Hormone Receptors To Enhance Their DNA Binding In Vitro and Transcriptional Activity in Mammalian Cells Mol. Cell. Biol., August 1, 1998; 18(8): 4471 - 4487. [Abstract] [Full Text]

				A. Z. Chaudhry, A. D. Vitullo, and R. M. Gronostajski Nuclear Factor I (NFI) Isoforms Differentially Activate Simple versus Complex NFI-responsive Promoters J. Biol. Chem., July 17, 1998; 273(29): 18538 - 18546. [Abstract] [Full Text] [PDF]

				J. M. Fitts, R. M. Klein, and C. A. Powers Comparison of Tamoxifen Effects on the Actions of Triiodothyronine or Growth Hormone in the Ovariectomized-Hypothyroid Rat J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 392 - 402. [Abstract] [Full Text]

				G. Sun, W. Porter, and S. Safe Estrogen-Induced Retinoic Acid Receptor {alpha}1 Gene Expression: Role of Estrogen Receptor-Sp1 Complex Mol. Endocrinol., June 1, 1998; 12(6): 882 - 890. [Abstract] [Full Text]

				Z. H. Yan, W. G. Karam, J. L. Staudinger, A. Medvedev, B. I. Ghanayem, and A. M. Jetten Regulation of Peroxisome Proliferator-activated Receptor alpha -Induced Transactivation by the Nuclear Orphan Receptor TAK1/TR4 J. Biol. Chem., May 1, 1998; 273(18): 10948 - 10957. [Abstract] [Full Text] [PDF]

				D. K. Scott, P.-E. Strömstedt, J.-C. Wang, and D. K. Granner Further Characterization of the Glucocorticoid Response Unit in the Phosphoenolpyruvate Carboxykinase Gene. The Role of the Glucocorticoid Receptor-Binding Sites Mol. Endocrinol., April 1, 1998; 12(4): 482 - 491. [Abstract] [Full Text]

				H. M. Chao, L. Y. Ma, B. S. McEwen, and R. R. Sakai Regulation of Glucocorticoid Receptor and Mineralocorticoid Receptor Messenger Ribonucleic Acids by Selective Agonists in the Rat Hippocampus Endocrinology, April 1, 1998; 139(4): 1810 - 1814. [Abstract] [Full Text] [PDF]

				E. K. Gass, S. A. Leonhardt, S. K. Nordeen, and D. P. Edwards The Antagonists RU486 and ZK98299 Stimulate Progesterone Receptor Binding to Deoxyribonucleic Acid in Vitro and in Vivo, but Have Distinct Effects on Receptor Conformation Endocrinology, April 1, 1998; 139(4): 1905 - 1919. [Abstract] [Full Text] [PDF]

				P. Aarnisalo, J. J. Palvimo, and O. A. Janne CREB-binding protein in androgen receptor-mediated signaling PNAS, March 3, 1998; 95(5): 2122 - 2127. [Abstract] [Full Text] [PDF]

				P. J. BARNES, S. PEDERSEN, and W. W. BUSSE Efficacy and Safety of Inhaled Corticosteroids . New Developments Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): S1 - 53. [Full Text] [PDF]

				R. H. DeKruyff, Y. Fang, and D. T. Umetsu Corticosteroids Enhance the Capacity of Macrophages to Induce Th2 Cytokine Synthesis in CD4+ Lymphocytes by Inhibiting IL-12 Production J. Immunol., March 1, 1998; 160(5): 2231 - 2237. [Abstract] [Full Text] [PDF]

				A. Revelli, M. Massobrio, and J. Tesarik Nongenomic Actions of Steroid Hormones in Reproductive Tissues Endocr. Rev., February 1, 1998; 19(1): 3 - 17. [Abstract] [Full Text]

				X. F. Ding, C. M. Anderson, H. Ma, H. Hong, R. M. Uht, P. J. Kushner, and M. R. Stallcup Nuclear Receptor-Binding Sites of Coactivators Glucocorticoid Receptor Interacting Protein 1 (GRIP1) and Steroid Receptor Coactivator 1 (SRC-1): Multiple Motifs with Different Binding Specificities Mol. Endocrinol., February 1, 1998; 12(2): 302 - 313. [Abstract] [Full Text]

				M J. Melia, N. Bofill, M. Hubank, and A. Meseguer Identification of Androgen-Regulated Genes in Mouse Kidney by Representational Difference Analysis and Random Arbitrarily Primed Polymerase Chain Reaction Endocrinology, February 1, 1998; 139(2): 688 - 695. [Abstract] [Full Text] [PDF]

				W. L. Kraus and J. T. Kadonaga p300 and estrogen receptor cooperatively activate transcription via differential enhancement of initiation and reinitiation Genes & Dev., February 1, 1998; 12(3): 331 - 342. [Abstract] [Full Text]