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BOR - Papers in Press, published online ahead of print July 9, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.015826
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Submitted January 24, 2003
Returned for revision February 22, 2003
Accepted June 26, 2003

Male Reproductive Tract


Role of Wilms' Tumor 1 (WT1) in the Transcriptional Regulation of the Mullerian-Inhibiting Substance Promoter

Anwar Hossain and Grady F. Saunders *

* To whom correspondence should be addressed. E-mail: gsaunders{at}odin.mdacc.tmc.edu.

Abstract
The Wilms' tumor 1 (WT1) gene product may regulate the MIS gene since mutations in WT1 can cause persistence of the mullerian duct in men. In this report we show by gel shift and chromatin immunoprecipitation assays that WT1 bound to a GC rich sequence in the murine Mis promoter. Mutation in this site abolished WT1-mediated activation of the Mis promoter. WT1, SOX9, and SF1 could synergistically activate the Mis promoter, and at least two factors were necessary for minimal activation. WT1 is essential factor for the activation of the Mis promoter and therefore the persistence of the mullerian duct in Denys-Drash syndrome patients may be due to de- regulation of the MIS gene.

Key words: Male Reproductive Tract • Gene regulation • Mullerian ducts


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