|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥2,200,000 (Direct Cost : ¥2,200,000)
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.