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Originally published In Press as doi:10.1074/jbc.M312574200 on December 17, 2003

J. Biol. Chem., Vol. 279, Issue 9, 7832-7839, February 27, 2004
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p300 Regulates the Synergy of Steroidogenic Factor-1 and Early Growth Response-1 in Activating Luteinizing Hormone-{beta} Subunit Gene*

Jean-François Mouillet, Christina Sonnenberg-Hirche, Xiaomei Yan, and Yoel Sadovsky{ddagger}

From the Departments of Obstetrics and Gynecology and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

Tight regulation of luteinizing hormone-{beta} subunit (LH{beta}) expression is critical for differentiation and maturation of mammalian sexual organs and reproductive function. Two transcription factors, steroidogenic factor-1 (SF-1) and early growth response-1 (Egr-1), play a central role in activating LH{beta} promoter, and the synergy between these two factors is essential in mediating gonadotropin-releasing hormone stimulation of LH{beta} promoter. Here we demonstrate that the transcriptional co-activator p300 regulates this synergy. Overexpression of p300 results in strong stimulation of LH{beta} promoter but only in the presence of both SF-1 and Egr-1, and not in the presence of other Egr proteins. Mutation of the binding sites for either SF-1 or Egr-1 completely abolishes the synergy between these two factors, as well as the influence of p300. Importantly, LH{beta} promoter is precipitated using p300 antibodies in a chromatin immunoprecipitation assay with L{beta}T2 gonadotropes, and this effect is enhanced by gonadotropin-releasing hormone. The influence of p300 on LH{beta} promoter is potentiated by steroid receptor co-activator, as well as by E1A proteins, and attenuated by Smad nuclear interacting protein 1. Taken together, these results suggest that p300 is recruited to LH{beta} promoter where it coordinates the functional synergy between SF-1 and Egr-1.


Received for publication, November 17, 2003

* This work was supported by National Institutes of Health grant R01 HD37571 (to Y. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: Dept. of Obstetrics and Gynecology, Washington University School of Medicine, 4566 Scott Ave., Campus Box 8064, St. Louis, MO 63110. Tel.: 314-747-0937; Fax: 314-747-1256; E-mail: sadovskyy{at}wustl.edu.


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