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J. Biol. Chem., Vol. 279, Issue 9, 7832-7839, February 27, 2004
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Subunit Gene*

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-
subunit (LH
) 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
promoter, and the synergy between these two factors is essential in mediating gonadotropin-releasing hormone stimulation of LH
promoter. Here we demonstrate that the transcriptional co-activator p300 regulates this synergy. Overexpression of p300 results in strong stimulation of LH
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
promoter is precipitated using p300 antibodies in a chromatin immunoprecipitation assay with L
T2 gonadotropes, and this effect is enhanced by gonadotropin-releasing hormone. The influence of p300 on LH
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
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.
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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