Molecular Clockwork

摘要

Although the basic transcriptional feedback loop that makes up the mammalian clock has been described, fundamental pieces of the clock's 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, (p. 1436) 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 complex (SIN3-HDAC) to the Perl promoter. The resulting histone deacetytation inhibits the transcription promoted by CLOCK-BMAL1. Depleting cells of PSF or SIN3-HDAC shortened the length of the circadian period, consistent with their roles as part of the fundamental clock mechanism.