Molecular cloning of cDNA encoding a novel microphthalmia-associated transcription factor isoform with a distinct amino-terminus

Nobuo Fuse, Ken Ichi Yasumoto, Kazuhisa Takeda, Shintaro Amae, Miki Yoshizawa, Tetsuo Udono, Kazuhiro Takahashi, Makoto Tamai, Yasushi Tomita, Masayoshi Tachibana, Shigeki Shibahara

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Microphthalmia-associated transcription factor (MITF) is a basic helix- loop-helix-leucine zipper protein, and plays an important role in the development of various cell types, such as neural-crest-derived melanocytes and optic-cup-derived retinal pigment epithelium. Three isoforms of MITF with distinct amino-termini have been described. These include melanocyte lineage- specific MITF-M, heart-type MITF-H, and the recently identified MITF-A. Here we identify a fourth isoform, MITF-C, with a unique amino-terminus of 34 amino acid residues, which shares about 43% sequence identity with putative transactivation segments of two previously identified leukemogenic factors, ENL and AF-9. Reverse transcription-polymerase chain reaction analysis revealed that MITF-C mRNA is expressed in many cell types, including retinal pigment epithelium, but is undetectable in melanocyte-lineage cells. In contrast, MITF-A and MITF-H mRNAs are coexpressed in all cell types examined. Transient cotransfection assays suggested that MITF-C, like other MITF isoforms, functions as a transcriptional activator of certain target genes, but its transactivation specificity for the target promoters is different from those of other MITF isoforms. Therefore, isoform multiplicity provides MITF with differential expression patterns as well as functional diversity.

Original languageEnglish
Pages (from-to)1043-1051
Number of pages9
JournalJournal of biochemistry
Volume126
Issue number6
DOIs
Publication statusPublished - 1999 Jan 1

Keywords

  • And Waardenburg syndrome
  • Melanocyte
  • Microphthalmia
  • Retinal pigment epithelium
  • Tyrosinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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