Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R).
Analysis of the nucleotide sequence of human melanocortin-1 receptor (MC1R) promoter indicated that an E-box (CANNTG) is present immediately upstream of the transcriptional initiation site. The presence of the CATGTG motif suggests that MC1R gene expression may be regulated by a basic helix-loop-helix-leucine-zipper (bHLH-LZ) type transcription factor. The microphthalmia-associated transcription factor (MITF), which belongs to the family of bHLH-LZ type transcription factors, regulates the transcription of melanogenesis-related enzyme genes such as the tyrosinase and TRP-1 genes. We investigated whether MITF regulates human MC1R gene expression through the same transcriptional mechanism as tyrosinase and TRP-1 genes in melanocytes. For this purpose, the effect of co-expression of cDNA encoding MITF on MC1R promoter activity in NIH/3T3 cells was studied. MC1R promoter activity was induced to the extent of approximately 5-fold in the presence of MITF. In addition, electrophoretic mobility shift assay indicated that nuclear extracts of human SK-Mel-2 cells contain a protein that binds specifically to the MC1R promoter region containing the CATGTG motif. These results suggested that MITF regulates not only the expression of enzymes involved in melanin synthesis, but also the expression of a receptor which plays an essential role in melanocyte functions.
Shiseido Research Center, 2-2-1 Hayabuchi, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8558, Japan.
Hirofumi
H
Aoki
Osamu
O
Moro
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D004586:Electrophoresis; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids / Q000235:genetics; D018043:Receptors, Corticotropin / Q000096:biosynthesis* / Q000235:genetics*; D044101:Receptors, Melanocortin; D013045:Species Specificity; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D015345:Oligonucleotide Probes; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D014157:Transcription Factors; D008156:Luciferases; D001616:beta-Galactosidase