Sci. Signal., 21 June 2011
Circadian Rhythms Molecular Clockwork
L. Bryan Ray
Science, Science Signaling, AAAS, Washington, DC 20005, USA
Although the basic transcriptional feedback loop that makes up the mammalian clock has been described, fundamental pieces of the clocks workings continue to be discovered. The oscillator depends on a transcriptional mechanism in which the transcription factor CLOCK-BMAL enhances transcription of its own inhibitor, PER. Duong et al. clarified the biochemical mechanism by which PER inhibits its own transcription by purifying proteins that associated with PER. The protein PSF, a transcriptional corepressor protein, was identified, which helped to recruit another protein, the SIN3–histone deacetylase (SIN3-HDAC) complex, to the Per1 promoter. The resulting histone deacetylation inhibits the transcription promoted by CLOCK-BMAL1. Depleting cells of PSF or the SIN3-HDAC complex shortened the length of the circadian period, consistent with their roles as part of the fundamental clock mechanism.
Citation: L. B. Ray, Molecular Clockwork. Sci. Signal. 4, ec176 (2011).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882