Regulation and differential expression of the c-maf gene in differentiating cultured cells.
The Maf transcription factors are involved in a variety of developmental and cellular differentiation processes, but their role in the differentiation of mesenchymal cells has not been described. Here, we have analyzed c-maf expression during the differentiation of adipocytes and muscle cells in cultured systems. The expression of c-maf mRNA was down-regulated during adipogenesis and up-regulated during myogenesis. In adipogenesis, the c-maf mRNA was down-regulated 58h after switching to the differentiation medium and just after PPARgamma2 mRNA was induced. A transient transfection analysis of a reporter gene containing the 5(')-flanking region of the c-maf gene showed that PPARgamma2 represses c-maf gene expression. We previously found that c-Maf, c-Jun, and Pax6 bind to and stimulate the c-maf gene. The PPARgamma2 repression of c-maf expression seems to be due, at least in part, to inhibition of the transactivation functions of c-Maf, c-Jun, and Pax6. The repression of c-maf was partly reversed by CBP, suggesting that these transcription factors compete for CBP or related transcription co-factors. In myogenesis, there was a differentiation-dependent stimulation of c-maf mRNA expression. The increased expression correlated with myoD expression. A transient transfection analysis showed that myoD stimulated a c-maf reporter gene through binding to two typical E-box elements located between 160 and 180 nucleotides upstream of the cap site. Binding of MyoD to the E-boxes was confirmed by a gel mobility shift assay and DNaseI footprinting analysis. Combined, these results suggest that the c-maf gene plays an important role during the differentiation of adipocyte and muscle cells from mesenchymal fibroblast cells.
Serria
Mohamed Saad
MS
Department of Biochemistry, Hokkaido University Graduate School of Medicine N15, W7, Kita-ku, Sapporo 060-8638, Japan.
Ikeda
Hiromi
H
Omoteyama
Kazuki
K
Hirokawa
Junich
J
Nishi
Shinzo
S
Sakai
Masaharu
M
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C495608:Maf protein, mouse; D017570:MyoD Protein; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D014157:Transcription Factors