Abstract
DEC1 is a transcription repressor that is induced by Hypoxia-Inducible Factor-α/β (HIF-α/β). 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-γ2 (PPARγ2) in 3T3-L1 cells. DEC1 did not prevent C/EBPβ, which is an upstream transactivator for PPARγ2, from occupying the PPARγ2 promoter. DEC1 occupied the PPARγ2 promoter by interacting with DNA-bound C/EBPβ. DEC1 occupancy was accompanied by a reduction of acetylated histones and an increase in histone deacetylase 1 (HDAC1) occupancy on the PPARγ2 promoter. Based on the fact that DEC1 interacts with HDAC1, this study suggests that DEC1 blocks adipogenesis by reinforcing HDAC1 recruitment to the PPARγ2 promoter. This study implies that DEC1 is one of the mediators that reset the pattern of PPARγ2 expression in response to hypoxia.