This Article Full Text Full Text (PDF) 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 Tremblay, J. J. Articles by Viger, R. S. Search for Related Content PubMed PubMed Citation Articles by Tremblay, J. J. Articles by Viger, R. S.

Modulation of Endogenous GATA-4 Activity Reveals Its Dual Contribution to Müllerian Inhibiting Substance Gene Transcription in Sertoli Cells

Ontogeny and Reproduction Research Unit, Centre Hospitalier de l’Université Laval (CHUL) Research Centre; and Centre for Research in Biology of Reproduction, Department of Obstetrics and Gynecology, Laval University, Ste-Foy, Quebec, Canada G1V 4G2

Address all correspondence and requests for reprints to: Dr. Robert S. Viger, Ontogeny and Reproduction Research Unit, T1–49, Centre Hospitalier de l’Université Laval (CHUL) Research Centre, 2705 Laurier Boulevard, Ste-Foy, Quebec, Canada G1V 4G2. E-mail: Robert.Viger{at}crchul.ulaval.ca

Secretion of Müllerian inhibiting substance by fetal Sertoli cells is essential for normal male sex differentiation since it induces regression of the Müllerian ducts in the developing male embryo. Proper spatiotemporal expression of the MIS gene requires a specific combination of transcription factors, including the zinc finger factor GATA-4 and the nuclear receptor steroidogenic factor-1, which both colocalize with Müllerian inhibiting substance in Sertoli cells. To establish the molecular mechanisms through which GATA-4 contributes to MIS transcription, we have generated and characterized novel GATA-4 dominant negative competitors. The first one, which consisted solely of the GATA-4 zinc finger DNA-binding domain, was an efficient competitor of GATA transcription mediated both by direct GATA binding to DNA and protein-protein interactions involving GATA factors. The second type of competitor consisted of the same GATA-4 zinc finger DNA-binding domain but harboring mutations that prevented DNA binding. This second class of competitors repressed GATA-dependent transactivation by specifically competing for GATA protein-protein interactions without affecting the DNA-binding activity of endogenous GATA factors. These competitors, along with the GATA-4 cofactor FOG-2 (friend of GATA-2), were used to specifically modulate endogenous GATA-4 activity in Sertoli cells. Our results indicate that GATA-4 contributes to MIS promoter activity through two distinct mechanisms. Moreover, the GATA competitors described here should provide invaluable in vitro and in vivo tools for the study of GATA- dependent transcription and the identification of new target genes.

This article has been cited by other articles:

				M. F. Bouchard, H. Taniguchi, and R. S Viger The effect of human GATA4 gene mutations on the activity of target gonadal promoters J. Mol. Endocrinol., February 1, 2009; 42(2): 149 - 160. [Abstract] [Full Text] [PDF]

				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]

				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]

				M. F. Bouchard, H. Taniguchi, and R. S. Viger Protein Kinase A-Dependent Synergism between GATA Factors and the Nuclear Receptor, Liver Receptor Homolog-1, Regulates Human Aromatase (CYP19) PII Promoter Activity in Breast Cancer Cells Endocrinology, November 1, 2005; 146(11): 4905 - 4916. [Abstract] [Full Text] [PDF]

				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]

				B. Ritz-Laser, A. Mamin, T. Brun, I. Avril, V. M. Schwitzgebel, and J. Philippe The Zinc Finger-Containing Transcription Factor Gata-4 Is Expressed in the Developing Endocrine Pancreas and Activates Glucagon Gene Expression Mol. Endocrinol., March 1, 2005; 19(3): 759 - 770. [Abstract] [Full Text] [PDF]

				C. Stocco In Vivo and in Vitro Inhibition of cyp19 Gene Expression by Prostaglandin F2{alpha} in Murine Luteal Cells: Implication of GATA-4 Endocrinology, November 1, 2004; 145(11): 4957 - 4966. [Abstract] [Full Text] [PDF]

				R. S. Viger, H. Taniguchi, N. M. Robert, and J. J. Tremblay The 25th Volume: Role of the GATA Family of Transcription Factors in Andrology J Androl, July 1, 2004; 25(4): 441 - 452. [Full Text] [PDF]

				H. A. LaVoie The Role of GATA in Mammalian Reproduction Experimental Biology and Medicine, December 1, 2003; 228(11): 1282 - 1290. [Abstract] [Full Text] [PDF]

				J. J. Tremblay and R. S. Viger A Mutated Form of Steroidogenic Factor 1 (SF-1 G35E) That Causes Sex Reversal in Humans Fails to Synergize with Transcription Factor GATA-4 J. Biol. Chem., October 24, 2003; 278(43): 42637 - 42642. [Abstract] [Full Text] [PDF]

				J. J. Tremblay and R. S. Viger Transcription Factor GATA-4 Is Activated by Phosphorylation of Serine 261 via the cAMP/Protein Kinase A Signaling Pathway in Gonadal Cells J. Biol. Chem., June 6, 2003; 278(24): 22128 - 22135. [Abstract] [Full Text] [PDF]

				M. Anttonen, I. Ketola, H. Parviainen, A.-K. Pusa, and M. Heikinheimo FOG-2 and GATA-4 Are Coexpressed in the Mouse Ovary and Can Modulate Mullerian-Inhibiting Substance Expression Biol Reprod, April 1, 2003; 68(4): 1333 - 1340. [Abstract] [Full Text] [PDF]

				C. Gillio-Meina, Y. Y. Hui, and H. A. LaVoie GATA-4 and GATA-6 Transcription Factors: Expression, Immunohistochemical Localization, and Possible Function in the Porcine Ovary Biol Reprod, February 1, 2003; 68(2): 412 - 422. [Abstract] [Full Text] [PDF]

				I.A.J. van Rooij, F.J.M. Broekmans, E.R. te Velde, B.C.J.M. Fauser, L.F.J.M.M. Bancsi, F.H.d. Jong, and A.P.N. Themmen Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve Hum. Reprod., December 1, 2002; 17(12): 3065 - 3071. [Abstract] [Full Text] [PDF]

				J. J. Tremblay, F. Hamel, and R. S. Viger Protein Kinase A-Dependent Cooperation between GATA and CCAAT/Enhancer-Binding Protein Transcription Factors Regulates Steroidogenic Acute Regulatory Protein Promoter Activity Endocrinology, October 1, 2002; 143(10): 3935 - 3945. [Abstract] [Full Text] [PDF]

				N. M. Robert, J. J. Tremblay, and R. S. Viger Friend of GATA (FOG)-1 and FOG-2 Differentially Repress the GATA-Dependent Activity of Multiple Gonadal Promoters Endocrinology, October 1, 2002; 143(10): 3963 - 3973. [Abstract] [Full Text] [PDF]

				R. C. Fowkes, P. King, and J. M. Burrin Regulation of Human Glycoprotein Hormone {alpha}-Subunit Gene Transcription in L{beta}T2 Gonadotropes by Protein Kinase C and Extracellular Signal-Regulated Kinase 1/2 Biol Reprod, September 1, 2002; 67(3): 725 - 734. [Abstract] [Full Text] [PDF]