A Functional Genomics Strategy Reveals Rora as a Component of the Mammalian Circadian Clock

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 sy...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2004-08, Vol.43 (4), p.527-537
Main Authors: Sato, Trey K., Panda, Satchidananda, Miraglia, Loren J., Reyes, Teresa M., Rudic, Radu D., McNamara, Peter, Naik, Kinnery A., FitzGerald, Garret A., Kay, Steve A., Hogenesch, John B.
Format: Article
Language:English
Subjects:
Animals
ARNTL Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
Biological Clocks - genetics
Circadian rhythm
Circadian Rhythm - genetics
Deoxyribonucleic acid
DNA
Gene expression
Genomics
Genomics - methods
HeLa Cells
Humans
Insects
Mammalia
Mice
Mice, Inbred C57BL
Mice, Neurologic Mutants
Mutation
Nuclear Receptor Subfamily 1, Group F, Member 1
Promoter Regions, Genetic
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid - biosynthesis
Receptors, Retinoic Acid - genetics
Response Elements - genetics
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Rodents
Trans-Activators
Transcription factors
Transcription Factors - genetics
Transcription Factors - metabolism
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Summary: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.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2004.07.018