A functional genomics strategy reveals rora as a component of the mammalian circadian clock

Trey K. Sato, Satchidananda Panda, Loren J. Miraglia, Teresa M. Reyes, Radu D. Rudic, Peter McNamara, Kinnery A. Naik, Garret A. Fitzgerald, Steve A. Kay, John B. Hogenesch

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)527-537
Number of pages11
JournalNeuron
Volume43
Issue number4
DOIs
Publication statusPublished - Aug 19 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sato, T. K., Panda, S., Miraglia, L. J., Reyes, T. M., Rudic, R. D., McNamara, P., ... Hogenesch, J. B. (2004). A functional genomics strategy reveals rora as a component of the mammalian circadian clock. Neuron, 43(4), 527-537. https://doi.org/10.1016/j.neuron.2004.07.018