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PPAR Research
Volume 2010 (2010), Article ID 352957, 17 pages
Research Article

The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver

1Centre de Recherche, INSERM U866, LBMN 6, Boulevard Gabriel, 21000 Dijon, France
2Laboratoire de Biochimie Métabolique et Nutritionnelle (LBMN), Faculté des Sciences Gabriel, Université de Bourgogne, 21000 Dijon, France
3INSERM U744, Laboratoire d'Épidémiologie et Santé Publique, Institut Pasteur de Lille, 1 Rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France
4Laboratory of Metabolism, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA
5Lady Davis Institute for Medical Research, McGill University, 3755 Côte Ste. Catherine Road, Montreal, QC, Canada H3T 1E2
6Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226-0509, USA
7Laboratoire de Pharmacologie et Toxicologie, UR66, INRA, 31931, Toulouse, France

Received 24 June 2010; Revised 1 December 2010; Accepted 9 December 2010

Academic Editor: Sander Kersten

Copyright © 2010 J. Chamouton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


PPARα and HNF4α are nuclear receptors that control gene transcription by direct binding to specific nucleotide sequences. Using transgenic mice deficient for either PPARα or HNF4α, 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 PPARα but not HNF4α transactivates. Intriguingly, we found that HNF4α enhanced PPARα/RXRα transactivation from TB PPRE3 in a DNA-binding independent manner. Coimmunoprecipitation assays supported the hypothesis that HNF4α was physically interacting with RXRα. RT-PCR performed with RNA from liver-specific HNF4α-null mice confirmed the involvement of HNF4α in the PPARα-regulated induction of Thb by Wy14,643. Overall, we conclude that HNF4α enhances the PPARα-mediated activation of Thb gene expression in part through interaction with the obligate PPARα partner, RXRα.