Hallsson Jón Hallsteinn, Haflidadóttir Benedikta S, Schepsky Alexander, Arnheiter Heinz, Steingrímsson Eiríkur
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101 Reykjavik, Iceland.
Pigment Cell Res. 2007 Jun;20(3):185-200. doi: 10.1111/j.1600-0749.2007.00373.x.
The microphthalmia-associated transcription factor (MITF) is a member of the MYC family of basic helix-loop-helix leucine zipper transcription factors. The corresponding gene was initially discovered in the mouse based on mutations which affect the development of several different cell types, including melanocytes and retinal pigment epithelium cells. Subsequently, it was shown to be associated with deafness and hypo-pigmentation disorders in humans. More recently, the gene has been shown to be critical in melanoma formation and to play a role in melanocyte stem cell maintenance. Thus, the mouse Mitf gene represents an important model system for the study of human disease as well as an interesting model for the study of transcription factor function in the organism. Here we use the evolutionary relationship of Mitf genes from numerous distantly related species, including vertebrates and invertebrates, to identify novel conserved domains in the Mitf protein and regions of possible functional importance in the 3' untranslated region. We also characterize the nine different 5' exons of the Mitf gene and identify a new 5' exon in the Drosophila Mitf gene. Our analysis sheds new light on the conservation of the Mitf gene and protein and opens the door for further functional analysis.
小眼畸形相关转录因子（MITF）是碱性螺旋-环-螺旋亮氨酸拉链转录因子MYC家族的成员。相应的基因最初是在小鼠中基于影响几种不同细胞类型（包括黑素细胞和视网膜色素上皮细胞）发育的突变而发现的。随后，它被证明与人类的耳聋和色素减退疾病有关。最近，该基因已被证明在黑色素瘤形成中至关重要，并在黑素细胞干细胞维持中发挥作用。因此，小鼠Mitf基因代表了研究人类疾病的重要模型系统，也是研究生物体中转录因子功能的有趣模型。在这里，我们利用来自众多远缘物种（包括脊椎动物和无脊椎动物）的Mitf基因的进化关系，来鉴定Mitf蛋白中的新保守结构域以及3'非翻译区中可能具有功能重要性的区域。我们还对Mitf基因的九个不同的5'外显子进行了表征，并在果蝇Mitf基因中鉴定出一个新的5'外显子。我们的分析为Mitf基因和蛋白的保守性提供了新的线索，并为进一步的功能分析打开了大门。
