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Role of Wilms Tumor 1 (WT1) in the Transcriptional Regulation of the Mullerian-Inhibiting Substance Promoter¹

Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009

The Wilms tumor 1 (WT1) gene product may regulate the mullerian-inhibiting substance (MIS) gene, because mutations in WT1 can cause persistence of the mullerian duct in men. In the present study, 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. The WT1, SRY box protein 9, and steroidogenic factor 1 could synergistically activate the Mis promoter, and at least two factors were necessary for minimal activation. The WT1 is an essential factor for activation of the Mis promoter; therefore, the persistence of the mullerian duct in patients with Denys-Drash syndrome may result from deregulation of the MIS gene.

¹ Supported by National Institutes of Health grants CA 34936 and CA 16672.

² Correspondence: Grady F. Saunders, Department of Biochemistry and Molecular Biology, Box-117, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030. FAX: 713 791 9478; gsaunders{at}odin.mdacc.tmc.edu

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