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First published online October 22, 2008

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REV-ERB – time for a change

Several sleep disorders are caused by the disruption of the circadian clock, which is underpinned by the fluctuating activity of transcription factors that periodically inhibit their own expression. The nuclear receptor REV-ERB, which is activated by heme binding, stabilises the clock by repressing Bmal1 transcription – but could REV-ERB be a good pharmacological target for circadian-rhythm disorders? On page 3629, Andrew Loudon and colleagues propose that it could. The authors use a FRET-based in vitro screen to identify a compound that promotes the formation of a complex between REV-ERB and the nuclear receptor co-repressor (NCoR). In fibroblasts expressing Bmal1 or Rev-erba, they show, the expression level of both genes oscillates. Importantly, the addition of the REV-ERB ligand causes phase shifts in BMAL1 and PER2 activity that change their directionality according to the phase of the circadian clock. Moreover, phase-dependent phase resetting also occurs in lung slices treated with the REV-ERB ligand. The authors propose that the binding of REV-ERB to endogenous ligands, such as heme, might be a mechanism of clock resetting; moreover, pharmacological modulation of REV-ERB might offer a novel approach to the treatment of circadian-rhythm disorders.

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Related articles in JCS:

Ligand modulation of REV-ERB function resets the peripheral circadian clock in a phasic manner

Qing Jun Meng, Andrew McMaster, Stephen Beesley, Wei Qun Lu, Julie Gibbs, Derek Parks, Jon Collins, Stuart Farrow, Rachelle Donn, David Ray, and Andrew Loudon
JCS 2008 121: 3629-3635. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?