Abstract
Circadian rhythms are thought to be generated by interlocked feedback loops of gene expression. Period (PER) proteins are essential components of the transcriptional feedback cycle and for phase-shifting the clock to different times of day, but the mechanism by which they repress transcription is not clear. Brown et al. have identified two PER-associated proteins, NONO and WDR5, that differentially modulate PER activity. NONO, an RNA-binding protein whose activity is essential for normal clock function, antagonizes PER-mediated repression. In contrast, WDR5, a histone methyltransferase adaptor, enhances PER-mediated repression. These regulatory proteins may impart resilience to the circadian oscillator in the face of fluctuations of clock components due to stochastic gene expression and environmental changes. S. A. Brown, J. Ripperger, S. Kadener, F. Fleury-Olela, F. Vilbois, M. Rosbash, U. Schibler, PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science 308 , 693-696 (2005). [Abstract] [Full Text]
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