Transcriptional activation of the melanocyte-specific genes by the human homolog of the mouse Microphthalmia protein.
Mi protein encoded at the mouse microphthalmia (mi) locus is a transcription factor with a basic helix-loop-helix/leucine zipper structure. To assess the function of the human homolog of Mi protein, termed microphthalmia-associated transcription factor (MITF), we analyzed the effects of MITF on the promoter function of the mouse tyrosinase and tyrosinase-related protein 1 (TRP-1) genes. These two gene promoters are able to direct transcription preferentially in melanin-producing cells, and an enhancer element M box of 11 bp, containing a CATGTG motif, is conserved in both promoters. By transient expression assays, we have localized the cis-acting element of the tyrosinase gene responsible for pigment cell-specific expression to the proximal 82-bp region, which contains a CATGTG motif (positions -12 to -7) but lacks the M box (positions -107 to -97). We also provide evidence that the 82-bp region and the M box are involved in the transactivation of the tyrosinase promoter by MITF and that the M box is bound by MITF in vitro. Furthermore, MITF activated the TRP-1 gene promoter possibly through the M box (positions -44 to -34). These results suggest that MITF is a common factor regulating transcription of the pigment cell-specific genes.
Yasumoto
K
K
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine.
Mahalingam
H
H
Suzuki
H
H
Yoshizawa
M
M
Yokoyama
K
K
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005982:Glutathione Transferase / Q000737:chemistry; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D008544:Melanocytes / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics; D010088:Oxidoreductases; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; C497234:MITF protein, human; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D011506:Proteins; D014157:Transcription Factors; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D005982:Glutathione Transferase