title: In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes.
abstract: Human epidermal melanocytes hold the full capacity for autocrine de novo synthesis/regulation/recycling of the essential cofactor 6-tetrahydrobiopterin (6BH(4)) for conversion of L-phenylalanine via phenylalanine hydroxylase to L-tyrosine and for production of L-Dopa via tyrosine hydroxylase to initiate both pigmentation and catecholamine synthesis in these neural crest-derived cells. Earlier we have demonstrated pterin-4a-carbinolamine dehydratase (PCD) mRNA and enzyme activities in epidermal melanocytes and keratinocytes. This protein dimerises also the transcription factor hepatocyte nuclear factor 1 (HNF-1), leading to activation of multiple genes. This study demonstrates for the first time DCoH/HNF-1 alpha expression and transcriptional activity in human epidermal melanocytes in vitro and in situ and identified tyrosinase, the key enzyme for pigmentation, as a new transcriptional target. Specific binding of DCoH/HNF-1 complex to the human tyrosinase promoter was confirmed by gel shift analysis. These results provide a novel mechanism in the regulation of skin pigmentation.
authors.affiliation: Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK. K.Schallreuter@bradford.ac.uk
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: Sonal
authors.initials: S
authors.lastname: Kothari
authors.forename: Sybille
authors.initials: S
authors.lastname: Hasse
authors.forename: Söbia
authors.initials: S
authors.lastname: Kauser
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Lindsey
authors.forename: Nicholas C J
authors.initials: NC
authors.lastname: Gibbons
authors.forename: Nigel
authors.initials: N
authors.lastname: Hibberts
authors.forename: John M
authors.initials: JM
authors.lastname: Wood
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D006836:Hydro-Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008544:Melanocytes / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D014442:Monophenol Monooxygenase; D006836:Hydro-Lyases; C076392:pterin-4a-carbinolamine dehydratase