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

被引:71
作者
Takeda, K
Yasumoto, K
Kawaguchi, N
Udono, T
Watanabe, K
Saito, H
Takahashi, K
Noda, M
Shibahara, S
机构
[1] Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Aoba Ku, Sendai, Miyagi 9808575, Japan
[2] Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 1010062, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION | 2002年 / 1574卷 / 01期
关键词
cell differentiation; macrophage; Mitf; osteoclast; retinal pigment epithelium; transcription;
D O I
10.1016/S0167-4781(01)00339-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (Blb 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 ID, which is located 3 kb upstream of the exon encoding the Blb 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. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:15 / 23
页数:9
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