Identification of a novel peroxisome proliferator-activated receptor (PPAR) γ promoter in man and transactivation by the nuclear receptor RORα1

PPAR gamma has been extensively studied for the past decade mainly due to its central role in promoting and maintaining the adipocyte phenotype. To date, three PPAR gamma isoforms have been described in man. Here we show the presence of a fourth PPAR gamma promoter with its cognate mRNA initiating at exon 1, as evidenced by primer extension analysis. The presence of a putative responsive element (RORE) for ROR alpha, a representative of the ROR/RZR orphan receptor superfamily, in the novel promoter was investigated. By gelshift experiments and site-directed mutagenesis we show that this RORE specifically binds the ROR alpha1 isoform. We further demonstrate that overexpression of ROR alpha1, but not the ROR alpha2 and ROR alpha3 isoforms, induced a 40-fold increase in promoter activity in transient transfection assays in various cell lines. Considering the strong transcriptional activation it is likely that ROR alpha1 forms a part of the multifactorial regulatory mechanisms that control expression of the human PPAR gamma gene. (C) 2001 Academic Press.