Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations
Mitf-D, a newly identified isoform, expressed in the retinal pigment epithelium and monocyte-lineage cells affected by Mitf mutations
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DOI：
10.1016/s0167-4781(01)00339-6
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发表时间：
2002-02-20
期刊：
影响因子：
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通讯作者：
Shibahara, S
中科院分区：
文献类型：
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作者：
Takeda, K;Yasumoto, K;Shibahara, S
小眼相关转录因子（Mitf）调节黑素细胞、视杯源性视网膜色素上皮（RPE）和某些类型的骨髓源性细胞的分化。Mitf由至少五个具有不同n端的同工异构体组成，每个同工异构体由一个单独的外显子1编码。在这里，我们发现了一种新的异构体，称为小鼠Mitf- d /人Mitf- d，它在RPE、巨噬细胞和受Mitf突变影响的破骨细胞中表达，但在其他Mitf靶细胞中不表达，包括黑素细胞系细胞和自然杀伤细胞。MITF- d的起始Met位于其他MITF异构体共享的下游结构域（Blb结构域）。MITF- d mRNA的5'-非翻译区由新发现的MITF基因的第一个外显子编码，称为外显子ID，位于编码Blb结构域的外显子上游3kb处。因此，MITF基因通过以细胞依赖的方式使用替代启动子产生具有不同表达模式的多个同种异构体。从而为MITF/ MITF突变体的表型变异性提供了分子基础。(C) 2002 Elsevier Science B.V.版权所有
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.