The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver. (15th December 2010)

• Record Type: Journal Article
• Authors: Chamouton, J.; Hansmannel, F.; Bonzo, J. A.; Clémencet, M. C.; Chevillard, G.; Battle, M.; Martin, P.; Pineau, T.; Duncan, S.; Gonzalez, F. J.; Latruffe, N.; Mandard, S.; Nicolas-Francès, V.
• Other Names: Kersten Sander Academic Editor.
• Is Part Of: PPAR research. Volume 2010(2010)
• Publication Date: 2010-12-15
• Subjects: Peroxisomes -- Periodicals; Peroxisomal disorders -- Periodicals; 571.65505
• DOI: 10.1155/2010/352957
• Languages: English
• ISSNs: 1687-4757

Abstract

Abstract : PPAR α and HNF4 α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPAR α or HNF4 α, we show that the expression of the peroxisomal 3-keto-acyl-CoA thiolase B ( Thb ) is under the dependence of these two transcription factors. Transactivation and gel shift experiments identified a novel PPAR response element within intron 3 of the Thb gene, by which PPAR α but not HNF4 α transactivates. Intriguingly, we found that HNF4 α enhanced PPAR α /RXR α transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4 α was physically interacting with RXR α . RT-PCR performed with RNA from liver-specific HNF4 α -null mice confirmed the involvement of HNF4 α in the PPAR α -regulated induction of Thb by Wy14, 643. Overall, we conclude that HNF4 α enhances the PPAR α -mediated activation of Thb gene expression in part through interaction with the obligate PPAR α partner, RXR α .