The orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1
Top Cited Papers
- 10 April 2005
- journal article
- research article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 12 (5) , 441-448
- https://doi.org/10.1038/nsmb925
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 RORα (NR1F1) directly activates transcription of Bmal1 through two conserved RORα response elements that are required for cell-autonomous transcriptional oscillation of Bmal1 mRNA. Positive involvement of RORα in generation of the Bmal1 circadian oscillation was verified by behavioral analyses of RORα-deficient staggerer mice that showed aberrant locomotor activity and unstable rhythmicity. In cultured cells, loss of endogenous RORα protein resulted in a dampened circadian rhythm of Bmal1 transcription, further indicating that RORα is a functional component of the cell-autonomous core circadian clock. These results indicate that RORα acts to promote Bmal1 transcription, thereby maintaining a robust circadian rhythm.Keywords
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