摘要：研究人员发现了驱动我们身体功能及行为的日常节律的哺乳动物生物钟的一个新的成分。 通过分析参与细胞内某种特别的生物化学负反馈回路（这是所有哺乳动物生物钟的基础）的蛋白质，Hao Duong及其同事发现了使这些生物钟能够精确走动的一个成分。 研究人员知道，一组叫做PER复合物的蛋白会以某种方式抑制另外一种叫做CLOCK-BMAL1的蛋白质，而这一抑制因此压制了那些原有的PER蛋白质的表达。 这种平衡性的行为在全身几乎所有的组织中都有发生，它为哺乳动物的生理学提供了每日的节律性脉动。 Duong及其他的研究人员发现了一种叫做PSF的蛋白质会在PER复合物内起作用以招募另外一种蛋白质（即sin3 -组蛋白去乙酰化酶复合物），后者会特异性地抑制CLOCK-BMAL1的活性。 研究人员经过实验发现，通过去除哺乳动物细胞中的PSF或sin3-组蛋白去乙酰化酶复合物，他们能够缩短生物钟周期的长度。 他们还提示，自真核细胞生物钟起源以来，这一生物化学的机制在进化的时候得到了保留。
生物探索推荐英文原文：
Getting at the gears of our circadian clocks
Researchers have identified a new piece of the mammalian circadian clock, which drives the daily rhythms of our bodily functions and behavior. By analyzing the proteins involved with a particular biochemical negative feedback loop in cells – the basis of all circadian rhythms in mammals – Hao Duong and colleagues have identified a component that helps these clocks keep accurate time. The researchers knew that a group of proteins known as the PER complex somehow inhibit the activity of a transcription factor, called CLOCK-BMAL1, and that this inhibition consequently represses the expression of those original PER proteins. This balancing act occurs in nearly all tissues throughout the body. Duong and the other researchers identified a protein known as PSF which works from within the PER complex to recruit another protein, the SIN3-histone deacetylase complex, which then specifically inhibits CLOCK-BMAL1 activity. The researchers found that they could shorten the length of the circadian cycle by removing PSF or SIN3-histone deacetylase complex from mammalian cells. They also suggest that this biochemical mechanism has been conserved over evolutionary time, since the actual origin of eukaryotic circadian clocks.
生物探索推荐英文论文摘要：
Science 17 June 2011:
Vol. 332 no. 6036 pp. 1436-1439
DOI: 10.1126/science.1196766
A Molecular Mechanism for Circadian Clock Negative Feedback
ABSTRACT
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.
