Glucocorticoid signaling synchronizes the liver circadian transcriptome.
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, HNF4alpha, as a mediator of circadian and glucocorticoid-regulated transcription, showing that it is a key conduit for downstream targeting.


CONCLUSIONS
We have demonstrated that by orchestrating transcriptional cascades, glucocorticoids are able to direct synchronization of a diverse range of functionally important circadian genes.
Reddy
Akhilesh B
AB
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, Cabridgeshire, UK. areddy@cantab.net
Maywood
Elizabeth S
ES
Karp
Natasha A
NA
King
Verdun M
VM
Inoue
Yusuke
Y
Gonzalez
Frank J
FJ
Lilley
Kathryn S
KS
Kyriacou
Charalambos P
CP
Hastings
Michael H
MH
D000818:Animals; D001483:Base Sequence; D001683:Biological Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D003907:Dexamethasone / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000378:metabolism* / Q000494:pharmacology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D008099:Liver / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010957:Plasmids; D015398:Signal Transduction / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D005938:Glucocorticoids; D051538:Hepatocyte Nuclear Factor 1-alpha; D003907:Dexamethasone