Analysis of the transcriptional regulation of the FABP2 promoter haplotypes by PPAR gamma/RXR alpha and Oct-1

作者：Boehme Mike; Nitz Inke; Doering Frank; Klapper Maja^*

来源：Biochimica et Biophysica Acta-Gene Regulatory Mechanisms, 2008, 1779(10): 616-621.

DOI：10.1016/j.bbagrm.2008.06.007

• FABP2
• PPARg
• Oct-1
• Promoter analysis
• EMSA

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 PPAR-gamma/RXR alpha 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 PPAR gamma/RXR alpha. In conclusion, our findings suggest a functional role of PPAR gamma/RXR alpha and Oct-1 in the regulation of the FABP2 gene.

• 出版日期2008-10