Hossain Anwar, Saunders Grady F
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Biol Reprod. 2003 Dec;69(6):1808-14. doi: 10.1095/biolreprod.103.015826. Epub 2003 Jul 9.
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.
威尔姆斯瘤1（WT1）基因产物可能调控抗苗勒管激素（MIS）基因，因为WT1的突变可导致男性苗勒管持续存在。在本研究中，我们通过凝胶迁移和染色质免疫沉淀试验表明，WT1与小鼠Mis启动子中富含GC的序列结合。该位点的突变消除了WT1介导的Mis启动子激活。WT1、SRY盒蛋白9和类固醇生成因子1可协同激活Mis启动子，且至少需要两个因子才能实现最小激活。WT1是激活Mis启动子的关键因子；因此，迪尼斯-德拉什综合征患者苗勒管的持续存在可能是由于MIS基因调控异常所致。
