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

Brown S.A., Ripperger J., Kadener S., Fleury-Olela F., Vilbois F., Rosbash M., Schibler U.

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.

Science 308:693-696(2005) [PubMed] [Europe PMC]

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