FIGURE 1.

Multiple roles of C/EBPβ during adipogenesis. Besides its well known function in the direct transactivation of C/EBPα and PPARγ, many new roles of C/EBPβ during adipogenesis have been revealed in the past decade. At the early stage of 3T3-L1 adipocyte differentiation, C/EBPβ transactivates the expression of multiple cell cycle-related genes to facilitate MCE, a required step for terminal adipocyte differentiation. A novel feed forward mechanism involving C/EBPβ and Kdm4b in the regulation of MCE is illustrated. Moreover, C/EBPβ transiently transactivates the expression of G9a, which delays the expression of C/EBPα and PPARγ, two anti-proliferation factors, so as to ensure MCE. The transactivation of Kdm4b (a histone demethylase) and G9a (a histone methyltransferase) by C/EBPβ provides evidence for the epigenetic control of MCE by C/EBPβ. At the late stage of 3T3-L1 adipocyte differentiation, C/EBPβ is involved in the activation of UPR and autophagy, through the transactivation of Xbp1 and Atg4b, respectively. In addition, C/EBPβ activates the expression of some other transcriptional factors and inhibits the expression of Wnt10b, an anti-adipogenic factor. Together, these effects ultimately lead to the activation or up-regulation of C/EBPα and PPARγ, thereby promoting terminal adipocyte differentiation. Black solid lines with arrowheads or blunt ends indicate transcriptional regulation of gene expression. Black dashed lines with arrowheads indicate promotion of activity. A black dashed line with a blunt end indicates inhibition of protein stability. Blue dashed lines with arrowheads indicate promotion of biological processes.