Identification of a novel peroxisome proliferator-activated receptor (PPAR) gamma promoter in man and transactivation by the nuclear receptor ROR alpha 1

PPAR gamma has been extensively studied for the past decade mainly due to i ts central role in promoting and maintaining the adipocyte phenotype. To da te, 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 a t exon 1, as evidenced by primer extension analysis. The presence of a puta tive responsive element (RORE) for ROR alpha, a representative of the ROR/R ZR orphan receptor superfamily, in the novel promoter was investigated. By gelshift experiments and site-directed mutagenesis we show that this RORE s pecifically binds the ROR alpha1 isoform. We further demonstrate that overe xpression of ROR alpha1, but not the ROR alpha2 and ROR alpha3 isoforms, in duced a 40-fold increase in promoter activity in transient transfection ass ays in various cell lines. Considering the strong transcriptional activatio n it is likely that ROR alpha1 forms a part of the multifactorial regulator y mechanisms that control expression of the human PPAR gamma gene. (C) 2001 Academic Press.