Regulation of pigment cell-specific gene expression by MITF

Melanocyte and retinal pigment epithelium (RPE) specifically express tyrosi nase and other melanin-producing enzymes, Microphthalmia-associated transcr iption factor (Mitf), encoded at the mouse microphthalmia locus, regulates the development and survival of many cell types, including melanocyte and R PE, MITF. the human homolog of Mitf, consists of at least four isoforms wit h distinct amino-termini, referred to as A, MITF-C, MITF-H, and MITF-M. MIT F-M is exclusively expressed in melanocytes and melanoma cells, and thus re presents the melanocyte lineage-specific isoform, In contrast, other isofor ms are expressed in many cell ta pes so far examined, These isoforms appear to function as transcriptional activators of the melanogenesis genes, as a ssessed by transient transfection assays in cultured cells, Functional sign ificance of Mitf-M in melanocyte differentiation mas verified by the molecu lar 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 r etrotransposable element in the intron between exon 3 and exon 4, leading t o complete repression of Mitf-M mRNA expression. Taken together, these resu lts suggest that melanogenesis in melanocyte and RPE is regulated hy separa te Mitf/MITF isoforms, Recent Endings on the multiplicity of MITF isoforms are summarized.