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Function of transcription factors mafs in the cellular differentiation

转录因子mafs在细胞分化中的作用

基本信息

批准号：
09680665
负责人：
SAKAI Masaharu
金额：
$ 2.11万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680665/
关键词：
Transcription factor Oncogene Differentiation maf Chondrocyte Lens Spinal code Kidney 脂肪細胞

项目摘要

maf is a family of oncogenes originally identified from avian oncogenic retrovirus, AS42, encoding a nuclear bZip transcription factor. We have isolated two maf related cDNA clones, maf-l(maf-B) and maf-2(c-maf), from a rat liver cDNA library. Both genes are expressed at low levels in a wide variety of rat tissue, including spleen, kidney, muscle and liver. Immunohistochemical studies and in situ hybridization analyses show that maf-1 and maf-2 are strongly expressed in the late stages of chondrocytes development in the femur epiphysis and the rib and limb cartilage of l5day old (E15) embryo in rat. In situ hybridization analyses of E15 embryos show both genes are expressed in the eye lens and the spinal cord as well as the cartilage. However, the expression patterns of maf-1 and maf-2 in lens and spinal cord were different. mafs are also expressed in developing kidney, maf-1 expressed in glomerular visceral epithelial and maf-2 expressed in renal tubules, and both expressions were never overlapped, In the differentiation process of the adipocytes, maf-2 expression was dramatically down regulated in differentiation specific manner. These results suggest that both transcription factors have closely related but different functions.Determination of specificity of the heterodimaer formation indicates that both factors significantly different properties and they might be have different target genes. Heterodimer formations of these factors dramatically change the specificity of DNA binding and transcriptional activity from that of homodimer. These findings suggest that cellular concentration and affinities of dimer formation of these factors might be very important for transcriptional modulation.The genomic clones of maf-l and maf-2 genes were isolated and the analyses of regulation of these genes show that auto regulation mechanism is worked on both genes.

maf是一个致癌基因家族，最初从禽致癌逆转录病毒AS42中发现，编码核bZip转录因子。我们从一个大鼠肝脏cDNA文库中分离出两个maf相关的cDNA克隆，maf- 1 （maf- b）和maf-2（c-maf）。这两种基因在包括脾脏、肾脏、肌肉和肝脏在内的多种大鼠组织中均以低水平表达。免疫组织化学研究和原位杂交分析表明，maf-1和maf-2在15日龄大鼠股骨骨骺和肋骨、肢体软骨软骨细胞发育后期强烈表达。E15胚胎的原位杂交分析显示，这两个基因在眼晶状体和脊髓以及软骨中都有表达。然而，maf-1和maf-2在晶状体和脊髓中的表达模式不同。maf-1表达于肾小球内脏上皮，maf-2表达于肾小管，两者表达不重叠。在脂肪细胞分化过程中，maf-2的表达以分化特异性的方式显著下调。这些结果表明，这两种转录因子具有密切相关但不同的功能。异二聚体形成特异性的测定表明，这两种因子的性质有显著差异，它们可能具有不同的靶基因。这些因子的异二聚体的形成显著地改变了DNA结合的特异性和转录活性，而不是同二聚体。这些发现表明，这些因子的细胞浓度和二聚体形成的亲和力可能对转录调节非常重要。分离到maf- 1和maf-2基因的基因组克隆，对这两个基因的调控分析表明，maf- 1和maf-2基因都有自调控机制。