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Molecular Endocrinology 11 (11): 1569-1580
Copyright © 1997 by The Endocrine Society

Functional Synergy between the Transcription Factor Sp1 and the Estrogen Receptor

W. Porter, B. Saville, D. Hoivik and S. Safe

Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, Texas 77843-4466

A GC-rich oligonucleotide containing an estrogen responsive element (ERE) half-site from the heat shock protein 27 (Hsp 27) gene promoter (-105 to -84) [i.e. GGGCGGG(N)10GGTCA; Sp1(N)10ERE] forms a complex with the Sp1 and estrogen receptor (ER) proteins. Moreover, promoter-reporter constructs containing this sequence (-108 to -84 or -108 to +23) are also estrogen-responsive. Mutation of the ERE half-site in the Hsp 27-derived oligonucleotides did not result in loss of estrogen responsiveness in transient transfection studies, suggesting that estrogen inducibility was mediated through the Sp1-DNA motif. Gel mobility shift assays using 32P-labeled wild type and ERE mutant Sp1(N)10ERE and consensus Sp1 oligonucleotides showed that Sp1 protein formed a DNA-protein complex with all three nucleotides, and the intensities of retarded bands were enhanced by coincubation with wild type ER and 11C-ER, which does not contain the DNA-binding domain. ER mutants in which N-terminal (19C-ER) and C-terminal (15C-ER) regions were deleted did not enhance Sp1-DNA binding or hormone-induced transactivation of GC-rich promoter-reporter constructs in ER-negative MDA-MB-231 cells, whereas both wild type and 11C-ER restored inducibility. Immunoprecipitation studies also confirmed that the Sp1 and ER proteins physically interact. The interaction of the Sp1 and ER proteins and the resulting enhanced Sp1-DNA binding is observed in the presence or absence of estrogen (hormone-independent), whereas transactivation of promoter-reporter constructs is estrogen-dependent. Thus, the results illustrate a new estrogen-dependent transactivation pathway that involves ER-protein interactions and is ERE-independent.




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Estrogen Up-Regulation of p53 Gene Expression in MCF-7 Breast Cancer Cells Is Mediated by Calmodulin Kinase IV-Dependent Activation of a Nuclear Factor {kappa}B/CCAAT-Binding Transcription Factor-1 Complex
Mol. Endocrinol., August 1, 2002; 16(8): 1793 - 1809.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
T. R. Ediger, S.-E. Park, and B. S. Katzenellenbogen
Estrogen Receptor Inducibility of the Human Na+/H+ Exchanger Regulatory Factor/Ezrin-Radixin-Moesin Binding Protein 50 (NHE-RF/EBP50) Gene Involving Multiple Half-Estrogen Response Elements
Mol. Endocrinol., August 1, 2002; 16(8): 1828 - 1839.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
P. Meisel
Cancer, genes and gender
Carcinogenesis, June 1, 2002; 23(6): 1087 - 1088.
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 J. Appl. Physiol.Home page
E. R. Levin
Genome and Hormones: Gender Differences in Physiology: Invited Review: Cell localization, physiology, and nongenomic actions of estrogen receptors
J Appl Physiol, October 1, 2001; 91(4): 1860 - 1867.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
S. Nilsson, S. Makela, E. Treuter, M. Tujague, J. Thomsen, G. Andersson, E. Enmark, K. Pettersson, M. Warner, and J.-A. Gustafsson
Mechanisms of Estrogen Action
Physiol Rev, October 1, 2001; 81(4): 1535 - 1565.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. G. V. Martini and B. S. Katzenellenbogen
Regulation of Prothymosin {alpha} Gene Expression by Estrogen in Estrogen Receptor-Containing Breast Cancer Cells via Upstream Half-Palindromic Estrogen Response Element Motifs
Endocrinology, August 1, 2001; 142(8): 3493 - 3501.
[Abstract] [Full Text] [PDF]

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 Nucleic Acids ResHome page
C. M. Klinge
Estrogen receptor interaction with estrogen response elements
Nucleic Acids Res., July 15, 2001; 29(14): 2905 - 2919.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Li, M. R. Briggs, T. E. Ahlborn, F. B. Kraemer, and J. Liu
Requirement of Sp1 and Estrogen Receptor {{alpha}} Interaction in 17{beta}-Estradiol-Mediated Transcriptional Activation of the Low Density Lipoprotein Receptor Gene Expression
Endocrinology, April 1, 2001; 142(4): 1546 - 1553.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
B. Morin, G. R. Woodcock, L. A. Nichols, and L. J. Holland
Heterodimerization between the Glucocorticoid Receptor and the Unrelated DNA-Binding Protein, Xenopus Glucocorticoid Receptor Accessory Factor
Mol. Endocrinol., March 1, 2001; 15(3): 458 - 466.
[Abstract] [Full Text]

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 EndocrinologyHome page
I. Samudio, C. Vyhlidal, F. Wang, M. Stoner, I. Chen, M. Kladde, R. Barhoumi, R. Burghardt, and S. Safe
Transcriptional Activation of Deoxyribonucleic Acid Polymerase {{alpha}} Gene Expression in MCF-7 Cells by 17{{beta}}-Estradiol
Endocrinology, March 1, 2001; 142(3): 1000 - 1008.
[Abstract] [Full Text] [PDF]

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 Physiol. Rev.Home page
J. E. Compston
Sex Steroids and Bone
Physiol Rev, January 1, 2001; 81(1): 419 - 447.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
M. Razandi, A. Pedram, and E. R. Levin
Plasma Membrane Estrogen Receptors Signal to Antiapoptosis in Breast Cancer
Mol. Endocrinol., September 1, 2000; 14(9): 1434 - 1447.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
O. Loudig, C. Babichuk, J. White, S. Abu-Abed, C. Mueller, and M. Petkovich
Cytochrome P450RAI(CYP26) Promoter: A Distinct Composite Retinoic Acid Response Element Underlies the Complex Regulation of Retinoic Acid Metabolism
Mol. Endocrinol., September 1, 2000; 14(9): 1483 - 1497.
[Abstract] [Full Text]

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 EndocrinologyHome page
T. Sugawara, M. Saito, and S. Fujimoto
Sp1 and SF-1 Interact and Cooperate in the Regulation of Human Steroidogenic Acute Regulatory Protein Gene Expression
Endocrinology, August 1, 2000; 141(8): 2895 - 2903.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
L. N. Petz and A. M. Nardulli
Sp1 Binding Sites and An Estrogen Response Element Half-Site Are Involved in Regulation of the Human Progesterone Receptor A Promoter
Mol. Endocrinol., July 1, 2000; 14(7): 972 - 985.
[Abstract] [Full Text]

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 EndocrinologyHome page
W. Xie, R. Duan, I. Chen, I. Samudio, and S. Safe
Transcriptional Activation of Thymidylate Synthase by 17{beta}-Estradiol in MCF-7 Human Breast Cancer Cells
Endocrinology, July 1, 2000; 141(7): 2439 - 2449.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
S. Misiti, S. Nanni, G. Fontemaggi, Y.-S. Cong, J. Wen, H. W. Hirte, G. Piaggio, A. Sacchi, A. Pontecorvi, S. Bacchetti, et al.
Induction of hTERT Expression and Telomerase Activity by Estrogens in Human Ovary Epithelium Cells
Mol. Cell. Biol., June 1, 2000; 20(11): 3764 - 3771.
[Abstract] [Full Text]

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 EndocrinologyHome page
L. Salvatori, L. Ravenna, M. P. Felli, M. R. Cardillo, M. A. Russo, L. Frati, A. Gulino, and E. Petrangeli
Identification of an Estrogen-Mediated Deoxyribonucleic Acid-Binding Independent Transactivation Pathway on the Epidermal Growth Factor Receptor Gene Promoter
Endocrinology, June 1, 2000; 141(6): 2266 - 2274.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
C. Lethimonier, G. Flouriot, Y. Valotaire, O. Kah, and B. Ducouret
Transcriptional Interference Between Glucocorticoid Receptor and Estradiol Receptor Mediates the Inhibitory Effect of Cortisol on Fish Vitellogenesis
Biol Reprod, June 1, 2000; 62(6): 1763 - 1771.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
A. van den Wijngaard, W. R. Mulder, R. Dijkema, C. J .C. Boersma, S. Mosselman, E. J. J. van Zoelen, and W. Olijve
Antiestrogens Specifically Up-Regulate Bone Morphogenetic Protein-4 Promoter Activity in Human Osteoblastic Cells
Mol. Endocrinol., May 1, 2000; 14(5): 623 - 633.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
S. Oesterreich, Q. Zhang, T. Hopp, S. A. W. Fuqua, M. Michaelis, H. H. Zhao, J. R. Davie, C. K. Osborne, and A. V. Lee
Tamoxifen-Bound Estrogen Receptor (ER) Strongly Interacts with the Nuclear Matrix Protein HET/SAF-B, a Novel Inhibitor of ER-Mediated Transactivation
Mol. Endocrinol., March 1, 2000; 14(3): 369 - 381.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
B. Saville, M. Wormke, F. Wang, T. Nguyen, E. Enmark, G. Kuiper, J.-A. Gustafsson, and S. Safe
Ligand-, Cell-, and Estrogen Receptor Subtype (alpha /beta )-dependent Activation at GC-rich (Sp1) Promoter Elements
J. Biol. Chem., February 25, 2000; 275(8): 5379 - 5387.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
H. Poukka, P. Aarnisalo, H. Santti, O. A. Janne, and J. J. Palvimo
Coregulator Small Nuclear RING Finger Protein (SNURF) Enhances Sp1- and Steroid Receptor-mediated Transcription by Different Mechanisms
J. Biol. Chem., January 7, 2000; 275(1): 571 - 579.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
S. Kyo, M. Takakura, T. Kanaya, W. Zhuo, K. Fujimoto, Y. Nishio, A. Orimo, and M. Inoue
Estrogen Activates Telomerase
Cancer Res., December 1, 1999; 59(23): 5917 - 5921.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
P. S. Jones, E. Parrott, and I. N. H. White
Activation of Transcription by Estrogen Receptor alpha and beta Is Cell Type- and Promoter-dependent
J. Biol. Chem., November 5, 1999; 274(45): 32008 - 32014.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. Dong, W. Wang, F. Wang, M. Stoner, J. C. Reed, M. Harigai, I. Samudio, M. P. Kladde, C. Vyhlidal, and S. Safe
Mechanisms of Transcriptional Activation of bcl-2 Gene Expression by 17beta -Estradiol in Breast Cancer Cells
J. Biol. Chem., November 5, 1999; 274(45): 32099 - 32107.
[Abstract] [Full Text] [PDF]

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 Mol. Endocrinol.Home page
R. Duan, W. Porter, I. Samudio, C. Vyhlidal, M. Kladde, and S. Safe
Transcriptional Activation of c-fos Protooncogene by 17{beta}-Estradiol: Mechanism of Aryl Hydrocarbon Receptor-Mediated Inhibition
Mol. Endocrinol., September 1, 1999; 13(9): 1511 - 1521.
[Abstract] [Full Text]

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 EndocrinologyHome page
S. C. Sharma, J. W. Clemens, M. D. Pisarska, and J. S. Richards
Expression and Function of Estrogen Receptor Subtypes in Granulosa Cells: Regulation by Estradiol and Forskolin
Endocrinology, September 1, 1999; 140(9): 4320 - 4334.
[Abstract] [Full Text]

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 Mol. Endocrinol.Home page
W. Wang, L. Dong, B. Saville, and S. Safe
Transcriptional Activation of E2F1 Gene Expression by 17{beta}-Estradiol in MCF-7 Cells Is Regulated by NF-Y-Sp1/Estrogen Receptor Interactions
Mol. Endocrinol., August 1, 1999; 13(8): 1373 - 1387.
[Abstract] [Full Text]

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 J. Biol. Chem.Home page
R. Ahlgren, G. Suske, M. R. Waterman, and J. Lund
Role of Sp1 in cAMP-dependent Transcriptional Regulation of the Bovine CYP11A Gene
J. Biol. Chem., July 2, 1999; 274(27): 19422 - 19428.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
D. S. Hunter, L. C. Hodges, P. M. Vonier, R. Fuchs-Young, M. M. Gottardis, and C. L. Walker
Estrogen Receptor Activation via Activation Function 2 Predicts Agonism of Xenoestrogens in Normal and Neoplastic Cells of the Uterine Myometrium
Cancer Res., July 1, 1999; 59(13): 3090 - 3099.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
C. Qin, P. Singh, and S. Safe
Transcriptional Activation of Insulin-Like Growth Factor-Binding Protein-4 by 17{beta}-Estradiol in MCF-7 Cells: Role of Estrogen Receptor-Sp1 Complexes
Endocrinology, June 1, 1999; 140(6): 2501 - 2508.
[Abstract] [Full Text]

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 EndocrinologyHome page
F. Machinal, M.-N. Dieudonne, M.-C. Leneveu, R. Pecquery, and Y. Giudicelli
In Vivo and in Vitro ob Gene Expression and Leptin Secretion in Rat Adipocytes: Evidence for a Regional Specific Regulation by Sex Steroid Hormones
Endocrinology, April 1, 1999; 140(4): 1567 - 1574.
[Abstract] [Full Text]


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