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是最初从禽致癌病毒AS42鉴定出的癌基因家族，编码了核BZIP转录因子。我们已经从大鼠肝脏cDNA文库中分离出两个与MAF相关的cDNA克隆MAF-L（MAF-B）和MAF-2（C-MAF）。这两个基因在各种大鼠组织中均以低水平表达，包括脾，肾脏，肌肉和肝脏。免疫组织化学研究和原位杂交分析表明，MAF-1和MAF-2在股骨epiphysis的软骨细胞发育的后期强烈表达，而大鼠中L5Day Old（E15）胚胎的肋骨和肢体软骨。 E15胚胎的原位杂交分析表明，这两个基因均在眼镜和脊髓以及软骨中表达。但是，镜头和脊髓中MAF-1和MAF-2的表达模式不同。 MAF在发育中以肾小球内脏上皮和肾小管中表达的MAF-2表达的肾脏，MAF-1表达，并且在脂肪细胞的分化过程中，这两种表达式从未重叠，MAF-2表达以差异化的特定方式下降。这些结果表明，这两个转录因子都有密切相关但功能不同。杂质形成的特异性确定表明，这两个因素的特性都显着不同，并且可能具有不同的靶基因。这些因素的异二聚体形成显着改变了同二聚体的DNA结合和转录活性的特异性。这些发现表明，这些因素的细胞浓度和二聚体形成的亲和力对于转录调节可能非常重要。分离了MAF-L和MAF-2基因的基因组克隆，并且调节这些基因的调节分析表明，自动调节机制在这两个基因上都起作用。