title: Regulation and differential expression of the c-maf gene in differentiating cultured cells.
abstract: 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.
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine N15, W7, Kita-ku, Sapporo 060-8638, Japan.
authors.forename: Mohamed Saad
authors.initials: MS
authors.lastname: Serria
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ikeda
authors.forename: Kazuki
authors.initials: K
authors.lastname: Omoteyama
authors.forename: Junich
authors.initials: J
authors.lastname: Hirokawa
authors.forename: Shinzo
authors.initials: S
authors.lastname: Nishi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sakai
mesh_terms: 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
chemical_list: 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