Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors.
Sox10 regulates melanocyte development at least partly through its stimulatory effect on Mitf gene expression. Here, we characterize the gene for dopachrome tautomerase (Dct/Trp2) as the second direct Sox10 target in melanocytes, arguing for the existence of Sox10 functions in melanocytes that are independent of its epistatic relationship to Mitf. Sox10 responsiveness was mediated by multiple binding sites within the proximal Dct/Trp2 promoter which display varying affinities and bind Sox10 monomers or dimers. Mitf synergistically enhanced Sox10-dependent activation of the Dct/Trp2 promoter. Synergy appears mechanistically complex and requires both direct binding of Sox10 to the promoter and the protein's transactivation domain.
Ludwig
Andreas
A
Institut für Biochemie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054, Erlangen, Germany.
Rehberg
Stephan
S
Wegner
Michael
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008544:Melanocytes / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D009154:Mutation; D009841:Oligonucleotides / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009841:Oligonucleotides; D011994:Recombinant Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors; D008156:Luciferases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase