PUBLICATION
Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids
- Authors
- Weger, B.D., Weger, M., Görling, B., Schink, A., Gobet, C., Keime, C., Poschet, G., Jost, B., Krone, N., Hell, R., Gachon, F., Luy, B., Dickmeis, T.
- ID
- ZDB-PUB-161215-20
- Date
- 2016
- Source
- PLoS Genetics 12: e1006512 (Journal)
- Registered Authors
- Dickmeis, Thomas, Weger, Benjamin, Weger, Meltem
- Keywords
- Gene expression, Circadian rhythms, Zebrafish, Circadian oscillators, Larvae, Gene regulation, Glutamine, Metabolic pathways
- Datasets
- GEO:GSE76073
- MeSH Terms
-
- Animals
- CLOCK Proteins/biosynthesis*
- CLOCK Proteins/genetics
- Circadian Clocks/genetics*
- Circadian Rhythm/genetics
- Citric Acid/metabolism
- E-Box Elements/genetics*
- Gene Expression Regulation
- Glucocorticoids/biosynthesis
- Glucocorticoids/deficiency
- Glucocorticoids/genetics*
- High-Throughput Nucleotide Sequencing
- Hormones/genetics
- Hormones/metabolism
- Humans
- Magnetic Resonance Spectroscopy
- Metabolic Networks and Pathways/genetics*
- Transcription, Genetic
- Transcriptome/genetics
- Urea/metabolism
- Zebrafish
- PubMed
- 27941970 Full text @ PLoS Genet.
- CTD
- 27941970
Citation
Weger, B.D., Weger, M., Görling, B., Schink, A., Gobet, C., Keime, C., Poschet, G., Jost, B., Krone, N., Hell, R., Gachon, F., Luy, B., Dickmeis, T. (2016) Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids. PLoS Genetics. 12:e1006512.
Abstract
Altered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping