Mouse γ-butyrobetaine dioxygenase is regulated by peroxisome proliferator-activated receptor α through a PPRE located in the proximal promoterReport as inadecuate




Mouse γ-butyrobetaine dioxygenase is regulated by peroxisome proliferator-activated receptor α through a PPRE located in the proximal promoter - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Justus-Liebig-Universität 2 MLU - Martin-Luther-Universität Halle Wittenberg

Abstract : Convincing evidence from studies with peroxisome proliferator-activated receptor PPARα-deficient mice suggested that the carnitine biosynthetic enzyme γ-butyrobetaine dioxygenase BBD is regulated by PPARα. However, the identification of BBD as a direct PPARα target gene as well as its exact regulation remained to be demonstrated. -analysis of the mouse BBD promoter revealed seven putative peroxisome proliferator response elements PPRE with high similarity to the consensus PPRE. Luciferase reporter gene assays using mutated and non-mutated serial 5′-truncation BBD promoter reporter constructs revealed that one PPRE located at -75 to -87 relative to the transcription start site in the proximal BBD promoter is probably functional. Using gel shift assays we observed -binding of PPARα-RXRα heterodimer to this PPRE confirming that it is functional. In conclusion, the present study clearly shows that mouse BBD is a direct PPARα target gene and that transcriptional up-regulation of mouse BBD by PPARα is likely mediated by binding of the PPARα-RXR heterodimer to one PPRE located in its proximal promoter region. The results confirm emerging evidence from recent studies that PPARα plays a key role in the regulation of carnitine homeostasis by controlling genes involved in both, carnitine synthesis and carnitine uptake.

Keywords : mouse. carnitine γ-butyrobetaine dioxygenase peroxisome proliferator-activated receptor α mouse





Author: Gaiping Wen - Hagen Kühne - Christine Rauer - Robert Ringseis - Klaus Eder -

Source: https://hal.archives-ouvertes.fr/



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