title: The Peroxisomal 3-keto-acyl-CoA thiolase B Gene Expression Is under the Dual Control of PPARα and HNF4α in the Liver.
abstract: 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.
authors: Centre de Recherche, INSERM U866, LBMN 6, Boulevard Gabriel, 21000 Dijon, France.
authors: J
authors: J
authors: Chamouton
authors: F
authors: F
authors: Hansmannel
authors: J A
authors: JA
authors: Bonzo
authors: M C
authors: MC
authors: Clémencet
authors: G
authors: G
authors: Chevillard
authors: M
authors: M
authors: Battle
authors: P
authors: P
authors: Martin
authors: T
authors: T
authors: Pineau
authors: S
authors: S
authors: Duncan
authors: F J
authors: FJ
authors: Gonzalez
authors: N
authors: N
authors: Latruffe
authors: S
authors: S
authors: Mandard
authors: V
authors: V
authors: Nicolas-Francès