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Updated: Jul 7, 2026

Annotation of Plant Gene Function via Combined Genomics, Metabolomics and Informatics
Published on: June 17, 2012
Shifted concentration dependency of EpRE- and XRE-mediated gene expression points at monofunctional EpRE-mediated
Yee Y Lee-Hilz1, Sovianne ter Borg, Willem J H van Berkel
1Laboratory of Biochemistry, Wageningen University, Dreijenlaan 3, 6703 HA Wageningen, The Netherlands; Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
Abstract:
Flavonoids are important bioactive compounds, omnipresent in the human diet, and are reported to be bifunctional inducers. These phytochemicals are able to induce xenobiotic-responsive element (XRE)- and electrophile-responsive element (EpRE)-mediated gene expression, resulting in the induction of biotransformation enzymes. To test whether flavonoid-induced EpRE-mediated gene expression could be the result of upstream XRE-mediated gene expression, several flavonoids were tested for their ability to induce XRE- and EpRE-mediated gene expression using two stably transfected reporter gene cell lines constructed in the same mouse Hepa-1c1c7 hepatoma background. Although classified as bifunctional inducers, all flavonoids were found to induce EpRE- and XRE-mediated gene expression in a different concentration range, which presents an issue not considered by the current definition of a bifunctional inducer. At physiological relevant concentrations, the induction of gene expression via the EpRE transcriptional enhancer element is dominant, leading in particular to elevated levels of EpRE-regulated detoxifying enzymes. Furthermore, these results strongly suggest that EpRE-mediated gene expression induced by flavonoids is not a downstream reaction of XRE-mediated gene expression.
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