文章基本信息

标题：The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription
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作者：Hong Sik Yoo ; Adrienne Rodriguez ; Dongjoo You 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：7
页码：1-17
DOI：10.1016/j.isci.2022.104564
语种：English
出版社：Elsevier
摘要：SummaryRetinoic acid (RA) counters insulin’s metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-inducedCYP26A1transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppressesCYP26A1expression, increasing RA’s elimination half-life. Interaction between CCAAT-enhancer-binding protein beta (C/EBPβ) and the major allele of SNP rs2068888 enhancesCYP26A1expression; the minor allele restricts the C/EBPβ effect onCYP26A1. The major and minor alleles associate with impaired human health or reduction in blood triglycerides, respectively. Thus, regulatingCYP26A1transcription contributes to adapting RA to coordinate energy availability with metabolism. These results enhance insight into CYP26A1 effects on RA during changes in energy status and glucocorticoid receptor modification of RAR-regulated gene expression.Graphical abstractDisplay OmittedHighlights•Glucocorticoids and glucagon increase liver retinoic acid concentrations during fasting•The glucocorticoid receptor binds to an RAR/RXR coactivation complex to reduceCYP26A1transcription•C/EBPβ binding to a major allele of SNP rs2068888 enhancesCYP26A1transcription•C/EBPβ binding to a minor allele of SNP rs2068888 inhibitsCYP26A1transcriptionBiochemistry; Biological sciences; Molecular biology