Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids

摘要: Altered daily patterns of hormone action are suspected to contribute metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones coordination global transcription and metabolism. Here, we examined diurnal metabolite transcriptome in a zebrafish deficiency model by RNA-Seq, NMR spectroscopy liquid chromatography-based methods. We observed dysregulation pathways including glutaminolysis, citrate urea cycles glyoxylate detoxification. Constant, non-rhythmic treatment rescued many these changes, with some notable exceptions among amino acid related pathways. Surprisingly, almost half entire dysregulated patterns. A combination E-box response elements enriched genes. This simple enhancer element sufficient drive rhythmic circadian reporter gene expression under exposure, revealing permissive function for glucocorticoid-dependent transcription. Our work highlights potentially contributing morbidity patients deficiency, even replacement therapy. Moreover, provide mechanistic insight into interaction between clock glucocorticoids transcriptional regulation