Journal
HEPATOLOGY
Volume 45, Issue 6, Pages 1478-1488Publisher
WILEY
DOI: 10.1002/hep.21571
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Funding
- Biotechnology and Biological Sciences Research Council [BB/C006941/1] Funding Source: researchfish
- Medical Research Council [MC_U105170643] Funding Source: researchfish
- MRC [MC_U105170643] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/C006941/1] Funding Source: Medline
- Medical Research Council [MC_U105170643] Funding Source: Medline
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Circadian control of physiology is mediated by local, tissue-based clocks, synchronized to each other and to solar time by signals from the suprachiasmatic nuclei (SCN), the master oscillator in the hypothalamus. These local clocks coordinate the transcription of key pathways to establish tissue-specific daily metabolic programs. How local transcriptomes are synchronized across the organism and their relative contribution to circadian output remain unclear. In the present study we showed that glucocorticoids alone are able to synchronize expression of about 60% of the circadian transcriptome. We propose that synchronization occurs directly by the action of glucocorticoids on a diverse range of downstream targets and indirectly by regulating the core clock genes mPer1, Bmal1, mCry1, and Dbp. We have identified the pivotal liver transcription factor, HNF4 alpha, as a mediator of circadian and glucocorticoid-regulated. transcription, showing that it is a key conduit for downstream targeting. Conclusion: We have demonstrated that by orchestrating transcriptional cascades, glucocorticoids are able to direct synchronization of a diverse range of functionally important circadian genes.
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