AIM: PPARgamma (peroxisome proliferator-activated receptor gamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulate the expression of genes associated with lipid metabolism. Herein, we show that expression levels of the novel PPARgamma transcript exhibit circadian oscillation. To study the mechanisms controlling PPARgamma expression, a novel PPARgamma gene promoter was cloned and characterized. METHODS: We analyzed the novel PPARgamma promoter by luciferase reporter assays and gel shift analysis. RESULTS: Surprisingly, it was not an intron but rather the novel first exon of PPARgamma that was found to have functional minimal promoter activity. Luciferase reporter assays and gel shift assays revealed that the novel first exon is essential for novel PPARgamma promoter activation and that DBP (albumin gene D-site binding protein) and E4BP4 (E4 promoter A binding protein 4) bind directly to D-sites in the novel first exon. CONCLUSION: Our results demonstrate that the PAR-bZIP (bZIP, basic leucine zipper) family and E4BP4 are the main regulatory factors involved in oscillation of novel PPARgamma expression. This regulatory mechanism clearly differs from that of the circadian expression of PPARalpha.
AIM: PPARgamma (peroxisome proliferator-activated receptor gamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulate the expression of genes associated with lipid metabolism. Herein, we show that expression levels of the novel PPARgamma transcript exhibit circadian oscillation. To study the mechanisms controlling PPARgamma expression, a novel PPARgamma gene promoter was cloned and characterized. METHODS: We analyzed the novel PPARgamma promoter by luciferase reporter assays and gel shift analysis. RESULTS: Surprisingly, it was not an intron but rather the novel first exon of PPARgamma that was found to have functional minimal promoter activity. Luciferase reporter assays and gel shift assays revealed that the novel first exon is essential for novel PPARgamma promoter activation and that DBP (albumin gene D-site binding protein) and E4BP4 (E4 promoter A binding protein 4) bind directly to D-sites in the novel first exon. CONCLUSION: Our results demonstrate that the PAR-bZIP (bZIP, basic leucine zipper) family and E4BP4 are the main regulatory factors involved in oscillation of novel PPARgamma expression. This regulatory mechanism clearly differs from that of the circadian expression of PPARalpha.
Authors: Liam A Finlay; Alex J Michels; Judy A Butler; Eric J Smith; Jeffrey S Monette; Régis F Moreau; Shay Kate Petersen; Balz Frei; Tory M Hagen Journal: Am J Physiol Regul Integr Comp Physiol Date: 2011-11-02 Impact factor: 3.619
Authors: Denuja Karunakaran; Adam W Turner; Anne-Claire Duchez; Sebastien Soubeyrand; Adil Rasheed; David Smyth; David P Cook; Majid Nikpay; Joshua W Kandiah; Calvin Pan; Michele Geoffrion; Richard Lee; Ludovic Boytard; Hailey Wyatt; My-Anh Nguyen; Paulina Lau; Markku Laakso; Bhama Ramkhelawon; Marcus Alvarez; Kirsi H Pietiläinen; Päivi Pajukanta; Barbara C Vanderhyden; Peter Liu; Scott B Berger; Peter J Gough; John Bertin; Mary-Ellen Harper; Aldons J Lusis; Ruth McPherson; Katey J Rayner Journal: Nat Metab Date: 2020-09-28