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

Members of the C/EBP family of transcription factors play essential roles i n the adipocyte differentiation program. Treatment of growth-arrested 3T3-L 1 preadipocytes with appropriate hormonal agents causes the cells to synchr onously reenter the cell cycle and to undergo mitotic clonal expansion. Exp ression of C/EBP beta and delta occur early in clonal expansion, later foll owed by C/EBP alpha (which is anti-mitotic) as the cells exit the cell cycl e begin to express adipocyte genes. C/EBP alpha serves as transcriptional a ctivator of many adipocyte genes whose expression produce the adipocyte phe notype. Recent work in this laboratory has focussed on the roles of C/EBP b eta and delta in the differentiation program, in particular the mechanisms by which they activate transcription of the C/EBP alpha gene. Several regul atory elements, both repressive and activating, in proximal promoter of the gene have been identified. The cognate transacting factors that interact w ith 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/EBP alpha gene and the terminal step s in the differentiation program. (C) 1999 Academic Press.