Role of Wilms tumor 1 (WT1) in the transcriptional regulation of the mullerian-inhibiting substance promoter

被引:39
作者
Hossain, A [1 ]
Saunders, GF [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA
关键词
gene regulation; male reproductive tract; mullerian ducts;
D O I
10.1095/biolreprod.103.015826
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1808 / 1814
页数:7
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