Identification of a distal enhancer for the melanocyte-specific promoter of the MITF gene

Ken Ichi Watanabe, Kazuhisa Takeda, Ken Ichi Yasumoto, Tetsuo Udono, Hideo Saito, Katsuhisa Ikeda, Tomonori Takasaka, Kazuhiro Takahashi, Toshimitsu Kobayashi, Masayoshi Tachibana, Shigeki Shibahara

研究成果: Article査読

56 被引用数 (Scopus)


Waardenburg syndrome (WS) is characterized by deafness and hypopigmentation because of the lack of melanocytes in the inner ear and skin. WS type 2 is associated with mutations in the gene encoding microphthalmia-associated transcription factor (MITF) that is required for melanocyte differentiation. MITF consists of multiple isoforms with different N-termini, one of which is exclusively expressed in melanocytes, named MITF-M. Its N-terminus is encoded by exon 1M that is under the regulation of the melanocyte-specific (M) promoter. Here we identify a distal regulatory region of 298 bp, located 14.5 kb upstream from exon 1M, which enhances the M promoter activity in cultured melanoma cells. This enhancer activity depends on the proximal M promoter region (-120 to -46). The MITF-M distal enhancer (MDE), thus identified, contains the binding sites for SOX10, a transcription factor responsible for another type of WS, known as Waardenburg-Hirschsprung syndrome. Characterization of MDE has suggested SOX10 as one of factors that are involved in the function of MDE. A putative MDE counterpart is located 12 kb upstream from mouse exon 1M and its role is discussed in relevance to the pathogenesis of red-eyed white Mitfmi-rw mice that exhibit small red eyes and white coat. Moreover, by in situ hybridization analysis, we suggest that Sox10 and Mitf-M (mRNA) are expressed in melanoblasts migrating toward the otic vesicle (prospective inner ear) of mouse embryos but are separately expressed in different cell types of the newborn cochlea. Thus, SOX10 regulates transcription from the M promoter in a developmental stage-specific manner.

ジャーナルPigment Cell Research
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • 農業および作物学
  • 植物科学
  • 発生生物学
  • 臨床生化学
  • 細胞生物学


「Identification of a distal enhancer for the melanocyte-specific promoter of the MITF gene」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。