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Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids

Weger, Benjamin D.; Weger, Meltem; Görling, Benjamin; Schink, Andrea; Gobet, Cédric; Keime, Céline; Poschet, Gernot; Jost, Bernard; Krone, Nils; Hell, Rüdiger; Gachon, Frédéric; Luy, Burkhard; Dickmeis, Thomas

Abstract (englisch):
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 glucocortico ... mehr


Zugehörige Institution(en) am KIT Institut für Biologische Grenzflächen (IBG)
Institut für Organische Chemie (IOC)
Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Jahr 2016
Sprache Englisch
Identifikator DOI: 10.1371/journal.pgen.1006512
ISSN: 1553-7404, 1553-7390
URN: urn:nbn:de:swb:90-635854
KITopen ID: 1000063585
HGF-Programm 47.01.01; LK 01
Erschienen in PLoS Genetics
Band 12
Heft 12
Seiten e1006512
Lizenz CC BY 4.0: Creative Commons Namensnennung 4.0 International
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
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