help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Molecular Endocrinology, doi:10.1210/me.2003-0342
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow NURSA Molecule Pages Link
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Flück, C. E.
Right arrow Articles by Miller, W. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Flück, C. E.
Right arrow Articles by Miller, W. L.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Molecular Endocrinology 18 (5): 1144-1157
Copyright © 2004 by The Endocrine Society

GATA-4 and GATA-6 Modulate Tissue-Specific Transcription of the Human Gene for P450c17 by Direct Interaction with Sp1

Christa E. Flück and Walter L. Miller

Department of Pediatrics and The Metabolic Research Unit, University of California San Francisco, San Francisco, California 94143-0978

Address all correspondence and requests for reprints to: Prof. Walter L. Miller, Department of Pediatrics, Building MR IV, Room 207, University of California San Francisco, San Francisco, California 94143-0978. E-mail: wlmlab{at}itsa.ucsf.edu.

Cytochrome P450c17 catalyzes steroidogenic 17{alpha}-hydroxylase and 17,20 lyase activities. Expression of the gene for P450c17 is cAMP dependent, tissue specific, developmentally programmed, and varies among species. Binding of Sp1, Sp3, and NF1-C (nuclear factor 1-C) to the first 227 bp of 5'flanking DNA (–227/LUC) is crucial for basal transcription in human NCI-H295A adrenal cells. Human placental JEG-3 cells contain Sp1, Sp3, and NF1, but do not express –227/LUC, even when transfected with a vector expressing steroidogenic factor 1 (SF-1). Therefore, other factors are essential for basal expression of P450c17. Deoxyribonuclease I footprinting and EMSAs identified a GATA consensus site at –64/–58 and an SF-1 site at –58/–50. RT-PCR identified GATA-4, GATA-6, and SF-1 in NCI-H295A cells and GATA-2 and GATA-3, but not GATA-4, GATA-6, or SF-1 in JEG-3 cells. Cotransfection of either GATA-4 or GATA-6 without SF-1 activated –227/LUC in JEG-3 cells, but cotransfection of GATA-2 or GATA-3 with or without SF-1 did not. Surprisingly, mutation of the GATA binding site in –227/LUC increased GATA-4 or GATA-6 induced activity, whereas mutation of the Sp1/Sp3 site decreased it. Furthermore, promoter constructs including the GATA site, but excluding the Sp1/Sp3 site at –196/–188, were not activated by GATA-4 or GATA-6, suggesting an interaction between Sp1/Sp3 and GATA-4 or GATA-6. Glutathione-S-transferase pull-down experiments and coimmunoprecipitation demonstrated interaction between GATA-4 or GATA-6 and Sp1, but not Sp3. Chromatin immunoprecipitation assays confirmed that this GATA-4/6 interaction with Sp1 occurred at the Sp site in the P450c17 promoter in NCI-H295A cells. Demethylation with 5-aza-2-deoxycytidine permitted JEG-3 cells to express endogenous P450c17, SF-1, GATA-4, GATA-6, and transfected –227/LUC. Thus, GATA-4 or GATA-6 and Sp1 together regulate expression of P450c17 in adrenal NCI-H295A cells and methylation of P450c17, GATA-4 and GATA-6 silence the expression of P450c17 in placental JEG-3 cells.

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1



This article has been cited by other articles:


Home page
 J EndocrinolHome page
E. Missaghian, P. Kempna, B. Dick, A. Hirsch, R. Alikhani-Koupaei, B. Jegou, P. E Mullis, B. M Frey, and C. E Fluck
Role of DNA methylation in the tissue-specific expression of the CYP17A1 gene for steroidogenesis in rodents
J. Endocrinol., July 1, 2009; 202(1): 99 - 109.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
G. Hua, B. Zhu, F. Rosa, N. Deblon, J. Adelaide, B. Kahn-Perles, D. Birnbaum, and J. Imbert
A Negative Feedback Regulatory Loop Associates the Tyrosine Kinase Receptor ERBB2 and the Transcription Factor GATA4 in Breast Cancer Cells
Mol. Cancer Res., March 1, 2009; 7(3): 402 - 414.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Shi, M. D. Schonemann, and S. H. Mellon
Regulation of P450c17 Expression in the Early Embryo Depends on GATA Factors
Endocrinology, February 1, 2009; 150(2): 946 - 956.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Yivgi-Ohana, N. Sher, N. Melamed-Book, S. Eimerl, M. Koler, P. R. Manna, D. M. Stocco, and J. Orly
Transcription of Steroidogenic Acute Regulatory Protein in the Rodent Ovary and Placenta: Alternative Modes of Cyclic Adenosine 3', 5'-Monophosphate Dependent and Independent Regulation
Endocrinology, February 1, 2009; 150(2): 977 - 989.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
B. Zhou, T. A. Francis, H. Yang, W. Tseng, Q. Zhong, B. Frenkel, Edward. E. Morrisey, David. K. Ann, P. Minoo, E. D. Crandall, et al.
GATA-6 mediates transcriptional activation of aquaporin-5 through interactions with Sp1
Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1141 - C1150.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
J. E Morabito, J. F Trott, D. M Korz, H. E Fairfield, S. H Buck, and R. C Hovey
A 5' distal palindrome within the mouse mammary tumor virus-long terminal repeat recruits a mammary gland-specific complex and is required for a synergistic response to progesterone plus prolactin
J. Mol. Endocrinol., August 1, 2008; 41(2): 75 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
D Bonofiglio, H Qi, S Gabriele, S Catalano, S Aquila, M Belmonte, and S Ando
Peroxisome proliferator-activated receptor {gamma} inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner
Endocr. Relat. Cancer, June 1, 2008; 15(2): 545 - 557.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando
Receptor-mediated tobacco toxicity: acceleration of sequential expression of {alpha}5 and {alpha}7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke
FASEB J, May 1, 2008; 22(5): 1356 - 1368.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. S. Viger, S. M. Guittot, M. Anttonen, D. B. Wilson, and M. Heikinheimo
Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease
Mol. Endocrinol., April 1, 2008; 22(4): 781 - 798.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
E. Samandari, P. Kempna, J.-M. Nuoffer, G. Hofer, P. E Mullis, and C. E Fluck
Human adrenal corticocarcinoma NCI-H295R cells produce more androgens than NCI-H295A cells and differ in 3{beta}-hydroxysteroid dehydrogenase type 2 and 17,20 lyase activities
J. Endocrinol., December 1, 2007; 195(3): 459 - 472.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. J. Kuhl, S. M. Ross, and K. W. Gaido
CCAAT/Enhancer Binding Protein {beta}, But Not Steroidogenic Factor-1, Modulates the Phthalate-Induced Dysregulation of Rat Fetal Testicular Steroidogenesis
Endocrinology, December 1, 2007; 148(12): 5851 - 5864.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. D. Shadley, K. Divakaran, K. Munson, R. N. Hines, K. Douglas, and D. G. McCarver
Identification and Functional Analysis of a Novel Human CYP2E1 Far Upstream Enhancer
Mol. Pharmacol., June 1, 2007; 71(6): 1630 - 1639.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. Kamnasaran, B. Qian, C. Hawkins, W. L. Stanford, and A. Guha
From the Cover: GATA6 is an astrocytoma tumor suppressor gene identified by gene trapping of mouse glioma model
PNAS, May 8, 2007; 104(19): 8053 - 8058.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Sher, N. Yivgi-Ohana, and J. Orly
Transcriptional Regulation of the Cholesterol Side Chain Cleavage Cytochrome P450 Gene (CYP11A1) Revisited: Binding of GATA, Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activating Protein (AP)-1 Proteins to a Distal Novel Cluster of cis-Regulatory Elements Potentiates AP-2 and Steroidogenic Factor-1-Dependent Gene Expression in the Rodent Placenta and Ovary
Mol. Endocrinol., April 1, 2007; 21(4): 948 - 962.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Rosa, C. Duff, M. Meyer, M. Lang-Muritano, G. Balercia, M. Boscaro, A. Kemal Topaloglu, R. Mioni, F. Fallo, L. Zuliani, et al.
P450c17 Deficiency: Clinical and Molecular Characterization of Six Patients
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1000 - 1007.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
P. Kempna, G. Hofer, P. E. Mullis, and C. E. Fluck
Pioglitazone Inhibits Androgen Production in NCI-H295R Cells by Regulating Gene Expression of CYP17 and HSD3B2
Mol. Pharmacol., March 1, 2007; 71(3): 787 - 798.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
E. B. Dammer, A. Leon, and M. B. Sewer
Coregulator Exchange and Sphingosine-Sensitive Cooperativity of Steroidogenic Factor-1, General Control Nonderepressed 5, p54, and p160 Coactivators Regulate Cyclic Adenosine 3',5'-Monophosphate-Dependent Cytochrome P450c17 Transcription Rate
Mol. Endocrinol., February 1, 2007; 21(2): 415 - 438.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. H. Mellon, S. R. Bair, C. Depoix, J.-L. Vigne, N. B. Hecht, and P. B. Brake
Translin Coactivates Steroidogenic Factor-1-Stimulated Transcription
Mol. Endocrinol., January 1, 2007; 21(1): 89 - 105.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
B. D. Looyenga and G. D. Hammer
Origin and Identity of Adrenocortical Tumors in Inhibin Knockout Mice: Implications for Cellular Plasticity in the Adrenal Cortex
Mol. Endocrinol., November 1, 2006; 20(11): 2848 - 2863.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Mao, W.-C. Tai, Y. Bai, C. Poizat, and A. S. Lee
In Vivo Regulation of Grp78/BiP Transcription in the Embryonic Heart: ROLE OF THE ENDOPLASMIC RETICULUM STRESS RESPONSE ELEMENT AND GATA-4
J. Biol. Chem., March 31, 2006; 281(13): 8877 - 8887.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
M. Bielinska, S. Kiiveri, H. Parviainen, S. Mannisto, M. Heikinheimo, and D. B. Wilson
Gonadectomy-induced Adrenocortical Neoplasia in the Domestic Ferret (Mustela putorius furo) and Laboratory Mouse.
Vet. Pathol., February 1, 2006; 43(2): 97 - 117.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. K. M. Ho, J. R. Wood, D. R. Stewart, K. Ewens, W. Ankener, J. Wickenheisser, V. Nelson-Degrave, Z. Zhang, R. S. Legro, A. Dunaif, et al.
Increased Transcription and Increased Messenger Ribonucleic Acid (mRNA) Stability Contribute to Increased GATA6 mRNA Abundance in Polycystic Ovary Syndrome Theca Cells
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6596 - 6602.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
L. J. Martin, H. Taniguchi, N. M. Robert, J. Simard, J. J. Tremblay, and R. S. Viger
GATA Factors and the Nuclear Receptors, Steroidogenic Factor 1/Liver Receptor Homolog 1, Are Key Mutual Partners in the Regulation of the Human 3{beta}-Hydroxysteroid Dehydrogenase Type 2 Promoter
Mol. Endocrinol., September 1, 2005; 19(9): 2358 - 2370.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. H. Bassett, B. Mayhew, K. Rehman, P. C. White, F. Mantero, G. Arnaldi, P. M. Stewart, I. Bujalska, and W. E. Rainey
Expression Profiles for Steroidogenic Enzymes in Adrenocortical Disease
J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5446 - 5455.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
Y.-H. Cheng and S. Handwerger
A Placenta-Specific Enhancer of the Human Syncytin Gene
Biol Reprod, September 1, 2005; 73(3): 500 - 509.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Huang, A. Dardis, and W. L. Miller
Regulation of Cytochrome b5 Gene Transcription by Sp3, GATA-6, and Steroidogenic Factor 1 in Human Adrenal NCI-H295A Cells
Mol. Endocrinol., August 1, 2005; 19(8): 2020 - 2034.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Tajima, K. Yoshii, S. Fukuda, M. Orisaka, K. Miyamoto, A. Amsterdam, and F. Kotsuji
Luteinizing Hormone-Induced Extracellular-Signal Regulated Kinase Activation Differently Modulates Progesterone and Androstenedione Production in Bovine Theca Cells
Endocrinology, July 1, 2005; 146(7): 2903 - 2910.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner
Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family
Endocr. Rev., June 1, 2005; 26(4): 525 - 582.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Huang and W. L. Miller
LBP Proteins Modulate SF1-Independent Expression of P450scc in Human Placental JEG-3 Cells
Mol. Endocrinol., February 1, 2005; 19(2): 409 - 420.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
K. J. Saner, T. Suzuki, H. Sasano, J. Pizzey, C. Ho, J. F. Strauss III, B. R. Carr, and W. E. Rainey
Steroid Sulfotransferase 2A1 Gene Transcription Is Regulated by Steroidogenic Factor 1 and GATA-6 in the Human Adrenal
Mol. Endocrinol., January 1, 2005; 19(1): 184 - 197.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
G. Vanpoucke, S. Goossens, B. De Craene, B. Gilbert, F. van Roy, and G. Berx
GATA-4 and MEF2C transcription factors control the tissue-specific expression of the {alpha}T-catenin gene CTNNA3
Nucleic Acids Res., August 9, 2004; 32(14): 4155 - 4165.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2004 by The Endocrine Society