Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations

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• 作者：Takeda ; Kazuhisa ; Yasumoto ; Ken-ichi ; Kawaguchi ; Naoko ; Udono ; Tetsuo ; Watanabe ; Ken-ichi ; et. al.
• 关键词：Cell differentiation ; Macrophage ; Mitf ; Osteoclast ; Retinal pigment epithelium ; Transcription
• 刊名：Biochimica et Biophysica Acta (BBA)/Gene Structure and Expression
• 出版年：2002
• 出版时间：February 20, 2002
• 年：2002
• 卷：1574
• 期：1
• 页码：15-23
• 全文大小：487 K

文摘

Microphthalmia-associated transcription factor (Mitf) regulates the differentiation of melanocytes, optic cup-derived retinal pigment epithelium (RPE), and some types of bone marrow-derived cells. Mitf consists of at least five isoforms with different N-termini, each of which is encoded by a separate exon 1. Here we identified a novel isoform, termed mouse Mitf-D/human MITF-D, that is expressed in RPE, macrophages, and osteoclasts affected by the Mitf mutations, but not expressed in other Mitf target cells, including melanocyte-lineage cells and natural killer cells. The initiation Met of MITF-D is located in the downstream domain (B1b domain) that is shared by other MITF isoforms. The 5′-untranslated region of MITF-D mRNA is encoded by the newly identified first exon of the MITF gene, termed exon 1D, which is located 3 kb upstream of the exon encoding the B1b domain. Thus, the MITF gene generates multiple isoforms with different expression patterns by using the alternative promoters in a cell-dependent manner, thereby providing the molecular basis for the phenotypic variability seen in the MITF/Mitf mutants.