Molecular basis of the structural and functional multiplicity of microphthalmia-associated transcription factor

Microphthalmia-associated transcription factor （MITF）影响许多类型的细胞，包括neural-crest derived melanocytes和optic cup-derived retinal pigment epithelium （RPE）。MITF-A、MITF-H、MITF-B和MITF-M的最少四个不同的因素，其氨基术语和表达模式的差异。这四个不同的框架分享了碳基末端移植，包括基本的螺旋环螺旋和精益拉链结构，其功能是转录激活器，由瞬态转染试验判断。人类MITF基因含有最少四个同位素-特定的第一个外显子，即外显子1A、1H、1B和1 M，在5'至3'方向上，每个编码给定同位素的唯一氨基终止符。这些异源特定外显子的5'闪烁区域是术语促发剂A、H、B和M，它们相应地显示了不同促发剂活动。促进者A Directs：RPE、神经性癌症和黑色素瘤细胞中报告基因表达的方向 ... More Promoter M只在黑色素瘤细胞中发挥功能。促进者H显示RPE和肿瘤细胞中的重要活动，但不在黑色素瘤细胞中。在对比度下，1.7-kb 5'-外显子1B显示在这些细胞线上没有明显的促进活动。因此，替代性的促进者提供了MITF基因在转录规则中的多样性和产生结构上不同的蛋白质同位素的能力。在添加中，随后的结果被发现。1.我们已经确定了第五个MITF-C同位素，在氨基终止和表达模式中的差异。2. Black-eyed white Mitfy D1mi-bw D1mice are characterized by the Complete white coat color and inner ear deafness due to lack of melanocytes and by normally pigmented RPE。The Molecular lesion of Mitf-D1 mi-bw D1 mice has been identified as the insertion of an L1 retrotransposable element in the intron 3 between exon 3和exon 4，导致Mitf-M mRNA表达的完整表达，并降低Mitf-A和Mitf-H mRNA表达的不同水平。因此， Mitf-M可以独立于黑色素细胞的正常发展，但不是RPE。Less（低）

Microphthalmia-associated transcription factor (MITF) affects the development of many types of cells, including neural-crest derived melanocytes and optic cup-derived retinal pigment epithelium (RPE). MITF consists of at least four isoforms, MITF-A, MITF-H, MITF-B and MITF-M, differing at their amino-termini and expression patterns. These four isoforms share the entire carboxyl-terminal portion, including a basic helix-loop-helix and leucine zipper structure, and function as transcriptional activators, as judged by transient transfection assay. The human MITF gene contains at least four isoform-specific first exons, exons 1A, 1H, 1B, and 1M in the 5' to 3' direction, each of which encodes the unique amino-terminus of a given isoform. The 5'-flanking regions of these isoform-specific exons are termed promoters A, H, B, and M, respectively, which showed different promoter activities. Promoter A directs the expression of a reporter gene in RPE, cervical cancer, and melanoma cells, whereas … More promoter M is functional only in melanoma cells. Promoter H showed the significant activity in RPE and cervical cancer cells but not in melanoma cells. In contrast, the 1.7-kb 5'-flanking region of exon 1B showed no noticeable promoter activity in these cell lines. Therefore, alternative promoters provide the MITF gene with the diversity in transcriptional regulation and the capability of generating structurally different protein isoforms.In addition, the following results have been obtained. 1. We have identified a fifth MITF isoform MITF-C, which differs in the amino-terminus and expression patterns. 2. Black-eyed white MitfィイD1mi-bwィエD1 mice are characterized by the complete white coat color and inner ear deafness due to lack of melanocytes and by normally pigmented RPE. The molecular lesion of MitfィイD1mi-bwィエD1 mice has been identified as the insertion of an L1 retrotransposable element in the intron 3 between exon 3 and exon 4, leading to complete repression of Mitf-M mRNA expression and to different levels of reduction of Mitf-A and Mitf-H mRNAs expression. Thus, Mitf-M is indispensable for the normal development of melanocytes but not RPE. Less