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. 2005 Apr 29;308(5722):693-6.
doi: 10.1126/science.1107373.

PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator

Steven A Brown  1 , Juergen Ripperger, Sebastian Kadener, Fabienne Fleury-Olela, Francis Vilbois, Michael Rosbash, Ueli Schibler
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PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator

Steven A Brown et al. Science. .

Abstract

The clock proteins PERIOD1 (PER1) and PERIOD2 (PER2) play essential roles in a negative transcriptional feedback loop that generates circadian rhythms in mammalian cells. We identified two PER1-associated factors, NONO and WDR5, that modulate PER activity. The reduction of NONO expression by RNA interference (RNAi) attenuated circadian rhythms in mammalian cells, and fruit flies carrying a hypomorphic allele were nearly arrhythmic. WDR5, a subunit of histone methyltransferase complexes, augmented PER-mediated transcriptional repression, and its reduction by RNAi diminished circadian histone methylations at the promoter of a clock gene.

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