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.