Structural organization of the human microphthalmia-associated transcription factor gene containing four alternative promoters

Tetsuo Udono, Ken Ichi Yasumoto, Kazuhisa Takeda, Shintaro Amae, Ken Ichi Watanabe, Hideo Saito, Nobuo Fuse, Masayoshi Tachibana, Kazuhiro Takahashi, Makoto Tamai, Shigeki Shibahara

研究成果: Article査読

123 被引用数 (Scopus)

抄録

Microphthalmia-associated transcription factor (MITF) affects the development of many types of cells, including melanocytes and retinal pigment epithelium (RPE). MITF consists of at least three isoforms, MITF-A, MITF-H and MITF-M, differing at their amino-termini and expression patterns. Here, we characterize the structural organization of the human MITF gene. The gene contains at least four isoform-specific first exons, exons 1A, 1H, 1B and 1M in the 5' to 3' direction, each of which encodes the unique amino-terminus of a given isoform, including newly identified MITF-B. The 5'-flanking regions of these isoform-specific exons are termed promoters A, H, B and M, respectively, which showed different promoter activities, as judged by transient transfection assay. Promoter A directs the expression of a reporter gene in RPE, cervical cancer and melanoma cells, whereas promoter M is functional only in melanoma cells. Promoter H showed the significant activity in RPE and cervical cancer cells but not in melanoma cells. In contrast, the 1.7 kb 5'-flanking region of exon 1B showed no noticeable promoter activity in these cell lines. Therefore, alternative promoters provide the MITF gene with the diversity in transcriptional regulation and the capability of generating structurally different protein isoforms. Copyright (C) 2000 Elsevier Science B.V.

本文言語English
ページ(範囲)205-219
ページ数15
ジャーナルBiochimica et Biophysica Acta - Gene Structure and Expression
1491
1-3
DOI
出版ステータスPublished - 2000 4月 25

ASJC Scopus subject areas

  • 構造生物学
  • 生物理学
  • 生化学
  • 遺伝学

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