J. Biochem, 1995, Vol. 118, No. 5 874-881
© 1995 Japanese Biochemical Society
Transcriptional Activation of the Melanocyte-Specific Genes by the Human Homolog of the Mouse Microphthalmia Protein1
Department of Applied Physiology and Molecular Biology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-77
4To whom correspondence should be addressed. Fax: +81-22-219-8423
Received November 18, 1994;
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Abstract |
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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.
gene regulation, melanogenesis, microphthalmia-associated transcription, factor, TRP-1, tyrosinase
1This work was supported in part by Grant-in-Aids for Encouragement of Young Scientists (to K-I.Y.), for Scientific Research on Priority Areas and for Developmental Scientific Research from the Ministry of Education, Science, and Culture of Japan.
2Department of Biochemistry and Molecular Biology, Marshall University School of Medicine, Huntington, WV 25755, USA
3Tohoku University Gene Research Center, Tsutsumidori-Amamiya-machi, Aoba-ku, Sendai, Miyagi 980
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