Transcriptional activation of the melanocyte-specific genes by the human homolog of the mouse Microphthalmia protein

Ken Ichi Yasumoto, Harish Mahalingam, Hiroyuki Suzuki, Miki Yoshizawa, Kouji Yokoyama, Shigeki Shibahara

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)874-881
Number of pages8
JournalJournal of biochemistry
Volume118
Issue number5
DOIs
Publication statusPublished - 1995 Oct

Keywords

  • Factor
  • Gene regulation
  • Melanogenesis
  • Microphthalmia-associated transcription
  • TRP-1
  • Tyrosinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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