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- Title
The orphan nuclear receptor RORaregulates 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 RORa(NR1F1) directly activates transcription of Bmal1 through two conserved RORaresponse elements that are required for cell-autonomous transcriptional oscillation of Bmal1 mRNA. Positive involvement of RORain generation of the Bmal1 circadian oscillation was verified by behavioral analyses of RORa-deficient staggerer mice that showed aberrant locomotor activity and unstable rhythmicity. In cultured cells, loss of endogenous RORaprotein resulted in a dampened circadian rhythm of Bmal1 transcription, further indicating that RORais a functional component of the cell-autonomous core circadian clock. These results indicate that RORaacts to promote Bmal1 transcription, thereby maintaining a robust circadian rhythm.
- Subjects
TRETINOIN; DERMATOLOGIC agents; RETINOIDS; HELIX-loop-helix motifs; TRANSCRIPTION factors; CIRCADIAN rhythms
- Publication
Nature Structural & Molecular Biology, 2005, Vol 12, Issue 5, p441
- ISSN
1545-9993
- Publication type
Article
- DOI
10.1038/nsmb925