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 ta pes 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 mas 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 LI 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 hy separate Mitf/MITF isoforms, Recent Endings on the multiplicity of MITF isoforms are summarized.