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 transcr iption factor with a basic helix-loop-helix/leucine zipper structure. To assess the function of the human homolog of Mi protein, termed micr ophthalmia-associated transcription factor (MITF), we analyzed the eff ects of MITF on the promoter function of the mouse tyrosinase and tyro sinase-related protein 1 (TRP-I) genes, These two gene promoters are a ble 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 fo r pigment cell-specific expression to the proximal 82-bp region, which contains a CATGTG motif (positions -12 to -7) but lacks the M box (po sitions -107 to -97). We also provide evidence that the 82-bp region a nd the M box are involved in the transactivation of the tyrosinase pro moter by MITF and that the M box is bound by MITF in vitro. Furthermor e, MITF activated the TRP-1 gene promoter possibly through the M box ( positions -44 to -34). These results suggest that MITF is a common fac tor regulating transcription of the pigment cell-specific genes.