Editors' ChoiceCircadian Rhythms

Molecular Clockwork

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Science Signaling  21 Jun 2011:
Vol. 4, Issue 178, pp. ec176
DOI: 10.1126/scisignal.4178ec176

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. 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.

H. A. Duong, M. S. Robles, D. Knutti, C. J. Weitz, A molecular mechanism for circadian clock negative feedback. Science 332, 1436–1439 (2011). [Abstract] [Full Text]

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