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- Title
The orphan nuclear receptor RORalpha regulates circadian transcription of the mammalian core-clock Bmal1.
- Authors
Akashi, Makoto; Takumi, Toru
- Abstract
The PAS (PER-ARNT-SIM) helix-loop-helix transcription factor BMAL1 (also known as MOP3) is an essential component of the circadian pacemaker in mammals. Here we show that the retinoic acid receptor-related orphan receptor RORalpha (NR1F1) directly activates transcription of Bmal1 through two conserved RORalpha response elements that are required for cell-autonomous transcriptional oscillation of Bmal1 mRNA. Positive involvement of RORalpha in generation of the Bmal1 circadian oscillation was verified by behavioral analyses of RORalpha-deficient staggerer mice that showed aberrant locomotor activity and unstable rhythmicity. In cultured cells, loss of endogenous RORalpha protein resulted in a dampened circadian rhythm of Bmal1 transcription, further indicating that RORalpha is a functional component of the cell-autonomous core circadian clock. These results indicate that RORalpha acts to promote Bmal1 transcription, thereby maintaining a robust circadian rhythm.
- Publication
Nature structural & molecular biology, 2005, Vol 12, Issue 5, p441
- ISSN
1545-9993
- Publication type
Journal Article
- DOI
10.1038/nsmb925