TY - JOUR
T1 - A functional genomics strategy reveals rora as a component of the mammalian circadian clock
AU - Sato, Trey K.
AU - Panda, Satchidananda
AU - Miraglia, Loren J.
AU - Reyes, Teresa M.
AU - Rudic, Radu D.
AU - McNamara, Peter
AU - Naik, Kinnery A.
AU - Fitzgerald, Garret A.
AU - Kay, Steve A.
AU - Hogenesch, John B.
N1 - Funding Information:
This research was supported by the Novartis Research Foundation (to S.P., L.J.M., K.A.N., and J.B.H.); a Rena and Victor Damone Postdoctoral Fellow Fellowship from the American Cancer Society (to T.K.S.); and National Institutes of Health grants (to T.M.R. and S.A.K.). This is manuscript 15692-CB of the Scripps Research Institute. We thank Pat Chappell, Steve Reppert, and Ron Evans for plasmids; Gene Yeh, Mary Frazer, Michelle Allen, Raquel McDowell, and Susana Pires for technical support; Tony Orth for informatic analysis; Jie Zhang and John Walker for microarray support; James Watson for tissue sectioning; Mary Morrison and Colin Fletcher for staggerer mice; Brooke Miller, Erin McDearmon, and Joe Takahashi for Clock total RNA; Michael Cooke, Sumit Chanda, and Josephine Harada for critical reading of this manuscript; and Marjory Givens, Sam Hazen, Andrew Liu, and members of the Kay lab for helpful advice.
PY - 2004/8/19
Y1 - 2004/8/19
N2 - The mammalian circadian clock plays an integral role in timing rhythmic physiology and behavior, such as locomotor activity, with anticipated daily environmental changes. The master oscillator resides within the suprachiasmatic nucleus (SCN), which can maintain circadian rhythms in the absence of synchronizing light input. Here, we describe a genomics-based approach to identify circadian activators of Bmal1, itself a key transcriptional activator that is necessary for core oscillator function. Using cell-based functional assays, as well as behavioral and molecular analyses, we identified Rora as an activator of Bmal1 transcription within the SCN. Rora is required for normal Bmal1 expression and consolidation of daily locomotor activity and is regulated by the core clock in the SCN. These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb α, which represses Bmal1 expression, are important in the maintenance of circadian clock function.
AB - The mammalian circadian clock plays an integral role in timing rhythmic physiology and behavior, such as locomotor activity, with anticipated daily environmental changes. The master oscillator resides within the suprachiasmatic nucleus (SCN), which can maintain circadian rhythms in the absence of synchronizing light input. Here, we describe a genomics-based approach to identify circadian activators of Bmal1, itself a key transcriptional activator that is necessary for core oscillator function. Using cell-based functional assays, as well as behavioral and molecular analyses, we identified Rora as an activator of Bmal1 transcription within the SCN. Rora is required for normal Bmal1 expression and consolidation of daily locomotor activity and is regulated by the core clock in the SCN. These results suggest that opposing activities of the orphan nuclear receptors Rora and Rev-erb α, which represses Bmal1 expression, are important in the maintenance of circadian clock function.
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U2 - 10.1016/j.neuron.2004.07.018
DO - 10.1016/j.neuron.2004.07.018
M3 - Article
C2 - 15312651
AN - SCOPUS:4143142003
SN - 0896-6273
VL - 43
SP - 527
EP - 537
JO - Neuron
JF - Neuron
IS - 4
ER -