A functional genomics strategy reveals Rora as a component of the mammalian circadian clock.
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Sato, Trey, Panda, Satchindananda, Miraglia, Loren, Reyes, Teresa, Rudic, Radu, Mcnamara, Peter, Naik, Kinnery, Fitzgerald, Garret, Kay, Steve and Hogenesch, John (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron, 43 (4). pp. 527-537. ISSN 0896-6273
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 alpha, which represses Bmal1 expression, are important in the maintenance of circadian clock function.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
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| Date Deposited: | 14 Dec 2009 14:02 |
| Last Modified: | 31 Jan 2013 01:22 |
| URI: | https://oak.novartis.com/id/eprint/269 |