Downregulation of repressive CUP/AP-2 isoforms during adipocyte differentiation

Activation of transcription of the C/EBP alpha (CCAAT/enhancer binding prot ein a) gene is a critical event in the differentiation of 3T3-L1 preadipocy tes into adipocytes. The kinetics of this process parallels a decline of AP -2 alpha protein (also referred to as CUP, C/EBP undifferentiated protein) and decreased binding of CUP/AP-2 alpha to the C/EBP alpha promoter. Mutati on of the CUP/AP-2 binding sites in the C/EBPa promoter results in increase d C/EBPa expression. Based on these findings, it appears that decline in AP -2a expression is an important early event in the adipocyte differentiation program. In the studies presented here, we identify three mRNAs that encod e the repressive CLTP/AP-2 alpha isoforms expressed in undifferentiated 3T3 -L1 preadipocytes. We demonstrate that the kinetics of the decline of these isoforms' expression over the course of differentiation parallels both the decrease in CUP/AP-2 alpha DNA binding activity and the increase in C/EBP alpha protein observed in previous studies. (C) 2001 Academic Press.