1. The transcription factor onecut-2 controls the microphthalmia-associated transcription factor gene.
- Author
-
Jacquemin P, Lannoy VJ, O'Sullivan J, Read A, Lemaigre FP, and Rousseau GG
- Subjects
- Animals, Binding Sites genetics, COS Cells, Cell Line, DNA Mutational Analysis, DNA-Binding Proteins genetics, Gene Expression drug effects, Homeodomain Proteins genetics, Homeodomain Proteins pharmacology, Humans, Melanocytes cytology, Microphthalmia-Associated Transcription Factor, Mutation, Promoter Regions, Genetic genetics, Transcription Factors genetics, Transcription Factors pharmacology, Transfection, DNA-Binding Proteins metabolism, Homeodomain Proteins metabolism, Melanocytes metabolism, Transcription Factors metabolism, Waardenburg Syndrome genetics
- Abstract
Microphthalmia-associated transcription factor (MITF) is essential for melanocyte differentiation. MITF mutations are associated with some cases of Waardenburg syndrome (WS) type 2. WS is a dominantly inherited disease characterized by auditory-pigmentary defects that result from the absence of melanocytes. The lack of mutation in MITF coding sequences in some WS2 patients suggests that unidentified factors controlling MITF expression might be involved. We show here that the cut-homeodomain transcription factor Onecut-2 (OC-2) is expressed in melanocytes and binds to the MITF gene promoter. Overexpression of OC-2 in transfected cells stimulates MITF promoter activity. Mutations that prevent OC-2 binding decrease MITF promoter activity by 75%. Based on these results, we searched in 56 WS2 patients for mutations in the OC2 gene or in OC-2 binding sites in the MITF promoter, but none was found. These results show that OC-2 stimulates MITF expression and that OC2 is a candidate gene, but not a common cause, of WS., (Copyright 2001 Academic Press.)
- Published
- 2001
- Full Text
- View/download PDF