Nature Structural & Molecular Biology12, 441 - 448 (2005)
Published online: 10 April 2005; | doi:10.1038/nsmb925
The orphan nuclear receptor ROR regulates circadian transcription of the mammalian core-clock Bmal1
Makoto Akashi
& Toru Takumi
Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Correspondence should be addressed to Toru Takumi takumi@obi.or.jp
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 ROR (NR1F1) directly activates transcription of Bmal1 through two conserved ROR response elements that are required for cell-autonomous transcriptional oscillation of Bmal1 mRNA. Positive involvement of ROR in generation of the Bmal1 circadian oscillation was verified by behavioral analyses of ROR-deficient staggerer mice that showed aberrant locomotor activity and unstable rhythmicity. In cultured cells, loss of endogenous ROR protein resulted in a dampened circadian rhythm of Bmal1 transcription, further indicating that ROR is a functional component of the cell-autonomous core circadian clock. These results indicate that ROR acts to promote Bmal1 transcription, thereby maintaining a robust circadian rhythm.
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regulates circadian transcription of the mammalian core-clock Bmal1
(NR1F1) directly activates transcription of Bmal1 through two conserved ROR
