Role of Wilms tumor 1 (WT1) in the transcriptional regulation of the Mullerian-inhibiting substance promoter.
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.
Hossain
Anwar
A
Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Saunders
Grady F
GF
D000818:Animals; D054304:Anti-Mullerian Hormone; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D030321:Denys-Drash Syndrome / Q000235:genetics; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D055758:SOX9 Transcription Factor; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology; D054339:Steroidogenic Factor 1; D013735:Testicular Hormones / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D025721:WT1 Proteins / Q000502:physiology*
D002843:Chromatin; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D006023:Glycoproteins; D006609:High Mobility Group Proteins; C515057:NR5A1 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D054339:Steroidogenic Factor 1; D013735:Testicular Hormones; D014157:Transcription Factors; D025721:WT1 Proteins; C515058:steroidogenic factor 1, mouse; D054304:Anti-Mullerian Hormone