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PERIOD1-Associated Proteins Modulate the Negative Limb of the Mammalian Circadian Oscillator
Ist Teil von
Science (American Association for the Advancement of Science), 2005-04, Vol.308 (5722), p.693-696
Ort / Verlag
Washington, DC: American Association for the Advancement of Science
Erscheinungsjahr
2005
Quelle
American Association for the Advancement of Science
Beschreibungen/Notizen
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.