Analysis of the transcriptional regulation of the FABP2 promoter haplotypes by PPARgamma/RXRalpha and Oct-1.
Variants of the human intestinal fatty acid binding protein 2 gene (FABP2) are associated with traits of the metabolic syndrome. Relevant FABP2 promoter polymorphisms c.-80_-79insT, c.-136_-132delAGTAG, c.-168_-166delAAGinsT, c.-260G>A, c.-471G>A, and c.-778G>T result in two haplotypes A and B. Activation of haplotypes by rosiglitazone stimulated PPARgamma/RXRalpha leads to 2-fold higher activity of haplotype B than A. As shown by chimeric FABP2 promoter constructs, the higher responsiveness of FABP2 haplotype B is mainly but not solely determined by polymorphism c.-471G>A. As shown by EMSA and promoter-reporter assays, Oct-1 interacts with the -471 region of FABP2 promoters, induces the activities of both FABP2 promoter haplotypes and abolishes the different activities of haplotypes induced by rosiglitazone activated PPARgamma/RXRalpha. In conclusion, our findings suggest a functional role of PPARgamma/RXRalpha and Oct-1 in the regulation of the FABP2 gene.
Böhme
Mike
M
Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, Kiel, Germany.
Nitz
Inke
I
Döring
Frank
F
Klapper
Maja
M
D001665:Binding Sites; D018938:Caco-2 Cells; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D050811:Octamer Transcription Factor-1 / Q000378:metabolism / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism / Q000502:physiology*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D047490:Retinoid X Receptor alpha / Q000378:metabolism / Q000502:physiology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D050811:Octamer Transcription Factor-1; D047495:PPAR gamma; D020033:Protein Isoforms; D047490:Retinoid X Receptor alpha; D045162:Thiazolidinediones; D000077154:Rosiglitazone