Title |
Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β
|
---|---|
Published in |
Nature, March 2012
|
DOI | 10.1038/nature11048 |
Pubmed ID | |
Authors |
Han Cho, Xuan Zhao, Megumi Hatori, Ruth T. Yu, Grant D. Barish, Michael T. Lam, Ling-Wa Chong, Luciano DiTacchio, Annette R. Atkins, Christopher K. Glass, Christopher Liddle, Johan Auwerx, Michael Downes, Satchidananda Panda, Ronald M. Evans |
Abstract |
The circadian clock acts at the genomic level to coordinate internal behavioural and physiological rhythms via the CLOCK-BMAL1 transcriptional heterodimer. Although the nuclear receptors REV-ERB-α and REV-ERB-β have been proposed to form an accessory feedback loop that contributes to clock function, their precise roles and importance remain unresolved. To establish their regulatory potential, we determined the genome-wide cis-acting targets (cistromes) of both REV-ERB isoforms in murine liver, which revealed shared recognition at over 50% of their total DNA binding sites and extensive overlap with the master circadian regulator BMAL1. Although REV-ERB-α has been shown to regulate Bmal1 expression directly, our cistromic analysis reveals a more profound connection between BMAL1 and the REV-ERB-α and REV-ERB-β genomic regulatory circuits than was previously suspected. Genes within the intersection of the BMAL1, REV-ERB-α and REV-ERB-β cistromes are highly enriched for both clock and metabolic functions. As predicted by the cistromic analysis, dual depletion of Rev-erb-α and Rev-erb-β function by creating double-knockout mice profoundly disrupted circadian expression of core circadian clock and lipid homeostatic gene networks. As a result, double-knockout mice show markedly altered circadian wheel-running behaviour and deregulated lipid metabolism. These data now unite REV-ERB-α and REV-ERB-β with PER, CRY and other components of the principal feedback loop that drives circadian expression and indicate a more integral mechanism for the coordination of circadian rhythm and metabolism. |
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United Kingdom | 1 | 13% |
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Japan | 1 | 13% |
Unknown | 4 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
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Science communicators (journalists, bloggers, editors) | 1 | 13% |
Scientists | 1 | 13% |
Practitioners (doctors, other healthcare professionals) | 1 | 13% |
Mendeley readers
Geographical breakdown
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Japan | 3 | <1% |
Portugal | 2 | <1% |
Brazil | 2 | <1% |
France | 2 | <1% |
Sweden | 2 | <1% |
Germany | 2 | <1% |
Netherlands | 2 | <1% |
Spain | 2 | <1% |
Other | 9 | 1% |
Unknown | 663 | 95% |
Demographic breakdown
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Researcher | 139 | 20% |
Student > Master | 88 | 13% |
Student > Bachelor | 61 | 9% |
Student > Doctoral Student | 30 | 4% |
Other | 117 | 17% |
Unknown | 93 | 13% |
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Biochemistry, Genetics and Molecular Biology | 129 | 19% |
Medicine and Dentistry | 74 | 11% |
Neuroscience | 42 | 6% |
Chemistry | 16 | 2% |
Other | 62 | 9% |
Unknown | 109 | 16% |