Regulation of pigment cell-specific gene expression by MITF.
Melanocyte and retinal pigment epithelium (RPE) specifically express tyrosinase and other melanin-producing enzymes. Microphthalmia-associated transcription factor (Mitf), encoded at the mouse microphthalmia locus, regulates the development and survival of many cell types, including melanocyte and RPE. MITF, the human homolog of Mitf, consists of at least four isoforms with distinct amino-termini, referred to as A, MITF-C, MITF-H, and MITF-M. MITF-M is exclusively expressed in melanocytes and melanoma cells, and thus represents the melanocyte lineage-specific isoform. In contrast, other isoforms are expressed in many cell types so far examined. These isoforms appear to function as transcriptional activators of the melanogenesis genes, as assessed by transient transfection assays in cultured cells. Functional significance of Mitf-M in melanocyte differentiation was verified by the molecular lesion of black-eyed white Mitf(mi-bw) mice, which lack melanocytes but have normal RPE. The Mitf gene of this mutant has the insertion of an L1 retrotransposable element in the intron between exon 3 and exon 4, leading to complete repression of Mitf-M mRNA expression. Taken together, these results suggest that melanogenesis in melanocyte and RPE is regulated by separate Mitf/MITF isoforms. Recent findings on the multiplicity of MITF isoforms are summarized.
Shibahara
S
S
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Miyagi, Japan. shibahar@mail.cc.tohoku.ac.jp
Yasumoto
K
K
Amae
S
S
Udono
T
T
Watanabe
K
K
Saito
H
H
Takeda
K
K
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D010858:Pigmentation / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D020033:Protein Isoforms; D014157:Transcription Factors