PERIOD1-Associated Proteins Modulate the Negative Limb of the Mammalian Circadian Oscillator

作者：Steven A. Brown, Juergen A. Ripperger, Sebastián Kadener, Fabienne Fleury-Olela, Francis Vilbois, Michael Rosbash, Ueli Schibler · 发表于：Science · 年份：2005 · DOI：10.1126/science.1107373 · 被引用次数：285 · 研究领域：Circadian rhythm and melatonin、Light effects on plants、Genetics, Aging, and Longevity in Model Organisms

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.