DEC1 is a transcription repressor that is induced by Hy-poxia-Inducible Factor-alpha/beta (HIF-alpha/beta). In this study, we found that either hypoxic treatment or ectopic expression of DEC1 blocks induction of a master adipogenic transactivator, peroxisome proliferative activated receptor-gamma2 (PPAR gamma 2) in 3T3-L1 cells. DEC1 did not prevent C/EBP beta, which is an upstream transactivator for PPAR gamma 2, from occupy-ing the PPARgamma2 promoter. DEC1 occupied the PPAR gamma 2 promoter by interacting with DNA-bound C/EBP beta. DEC1 occupancy was accompanied by a reduction of acetylated histones and an increase in histone deacetylase 1 (HDAC1) occupancy on the PPAR gamma 2 promoter. Based on the fact that DEC1 interacts with HDAC1, this study suggests that DEC1 blocks adipogenesis by reinforcing HDAC1 recruitment to the PPAR gamma 2 promoter. This study implies that DEC1 is one of the mediators that reset the pattern of PPAR gamma 2 expression in response to hypoxia.

Keywords: adipogenesis, C/EBP beta, DEC1, hypoxia, PPAR gamma