In situ and in vitro evidence for DCoH/HNF-1 alpha transcription of tyrosinase in human skin melanocytes.
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.
Schallreuter
Karin U
KU
Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK. K.Schallreuter@bradford.ac.uk
Kothari
Sonal
S
Hasse
Sybille
S
Kauser
Söbia
S
Lindsey
Nigel J
NJ
Gibbons
Nicholas C J
NC
Hibberts
Nigel
N
Wood
John M
JM
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
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