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Science. 2005 Apr 29;308(5722):693-6.

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

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Department of Molecular Biology and National Centres of Competence in Research (NCCR) Frontiers in Genetics, Sciences III, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland.


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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