A Big Gene Linked to Small Eyes Encodes Multiple Mitf Isoforms: Many Promoters Make Light Work

Ken Ichi Yasumoto, Shintaro Amae, Tetsuo Udono, Nobuo Fuse, Kazuhisa Takeda, Shigeki Shibahara

Research output: Contribution to journalReview articlepeer-review

70 Citations (Scopus)

Abstract

Among more than 80 different loci related to mouse coat color, microphthalmia-associated transcription factor (Mitf) encoded at the mouse microphthalmia locus is one of the most exciting molecules that regulates the development and survival of many cell types, including melanocyte, retinal pigment epithelium (RPE), and mast cells. Mitf and its human homolog MITF consist of at least three isoforms, referred to as Mitf-A/MITF-A, the heart-type Mitf-H/MITF-H, and the melanocyte lineage-specific Mitf-M/MITF-M, respectively. These isoforms differ in the amino-terminal domains but share a transactivation domain and a basic helix-loop-helix and leucine-zipper structure that is required for DNA binding and dimerization. MITF-M is exclusively expressed in melanocytes and melanoma cells, but not in other cell types, including RPE cells. In contrast, MITF-A mRNA is widely expressed in many cell types. These three isoform mRNAs are possibly generated by differential usage of the gene promoters and by alternative splicing. We predict that the entire MITF gene spans about 200 kb of DNA. Like MITF-M, MITF-A is able to activate the two melanogenesis gene promoters, tyrosinase and tyrosinase-related protein 1. These results suggest that melanogenesis may be regulated by different MITF isoforms in melanocyte and RPE. Possible implications of the multiplicity in Mitf/MITF isoforms are discussed.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalPigment Cell Research
Volume11
Issue number6
DOIs
Publication statusPublished - 1998 Dec

Keywords

  • Differentiation
  • Melanocyte
  • Microphthalmia
  • Retinal Pigment epithelium

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science
  • Developmental Biology
  • Clinical Biochemistry
  • Cell Biology

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