Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation

Members of the C/EBP family of transcription factors play essential roles in the adipocyte differentiation program. Treatment of growth-arrested 3T3-L1 preadipocytes with appropriate hormonal agents causes the cells to synchronously reenter the cell cycle and to undergo mitotic clonal expansion. Expression of C/EBPbeta and delta occur early in clonal expansion, later followed by C/EBPalpha (which is anti-mitotic) as the cells exit the cell cycle begin to express adipocyte genes. C/EBPalpha serves as transcriptional activator of many adipocyte genes whose expression produce the adipocyte phenotype. Recent work in this laboratory has focussed on the roles of C/EBPbeta and delta in the differentiation program, in particular the mechanisms by which they activate transcription of the C/EBPalpha gene. Several regulatory elements, both repressive and activating, in proximal promoter of the gene have been identified. The cognate transacting factors that interact with these elements have been characterized and their functions elucidated. These factors have been incorporated into a model for a cascade that leads to transcriptional activation of the C/EBPalpha gene and the terminal steps in the differentiation program.