The orphan nuclear receptor DAX-1 acts as a novel transcriptional corepressor of PPARγ

DAX-1 is an atypical nuclear receptor (NR) which functions primarily as a transcriptional corepressor of other NRs via heterodimerization. Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-dependent NR which performs a key function in adipogenesis. In this study, we evaluated a novel cross-talk mechanism between DAX-1 and PPAR gamma. Transient transfection assays demonstrated that DAX-1 inhibits the transactivity of PPAR gamma in a dose-dependent manner. DAX-1 directly competed with the PPAR gamma coactivator (PGC)-1 alpha for binding to PPAR gamma. Endogenous levels of DAX-1 were significantly lower in differentiated 3T3-L1 adipocytes as compared to preadipocytes. Using a retroviral expression system, we demonstrated that DAX-1 overexpression downregulates the expression of PPAR gamma target genes, resulting in an attenuation of adipogenesis in 3T3-L1 cells. Our results suggest that DAX-1 acts as a corepressor of PPAR gamma and performs a potential function in the regulation of PPAR gamma-mediated cellular differentiation. (C) 2008 Elsevier Inc. All rights reserved.