A Molecular Mechanism for Circadian Clock Negative Feedback

被引：228

作者：

Duong, Hao A. ^{[1
]}

Robles, Maria S. ^{[1
]}

Knutti, Darko ^{[1
]}

Weitz, Charles J. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

来源：

SCIENCE | 2011年 / 332卷 / 6036期

基金：

瑞士国家科学基金会;

关键词：

HISTONE ACETYLATION; TRANSCRIPTION; BINDING; PSF; COMPONENTS; REVEALS; FBXL3; MPER1; LOOP; LIMB;

D O I：

10.1126/science.1196766

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Circadian rhythms in mammals are generated by a feedback loop in which the three PERIOD (PER) proteins, acting in a large complex, inhibit the transcriptional activity of the CLOCK-BMAL1 dimer, which represses their own expression. Although fundamental, the mechanism of negative feedback in the mammalian clock, or any eukaryotic clock, is unknown. We analyzed protein constituents of PER complexes purified from mouse tissues and identified PSF (polypyrimidine tract-binding protein-associated splicing factor). Our analysis indicates that PSF within the PER complex recruits SIN3A, a scaffold for assembly of transcriptional inhibitory complexes and that the PER complex thereby rhythmically delivers histone deacetylases to the Per1 promoter, which repress Per1 transcription. These findings provide a function for the PER complex and a molecular mechanism for circadian clock negative feedback.

引用

页码：1436 / 1439

页数：4

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