Dibner Charna, Sage Daniel, Unser Michael, Bauer Christoph, d'Eysmond Thomas, Naef Felix, Schibler Ueli
Department of Molecular Biology & NCCR Frontiers in Genetics, University of Geneva, Geneva, Switzerland.
EMBO J. 2009 Jan 21;28(2):123-34. doi: 10.1038/emboj.2008.262. Epub 2008 Dec 11.
Mammalian circadian oscillators are considered to rely on transcription/translation feedback loops in clock gene expression. The major and essential loop involves the autorepression of cryptochrome (Cry1, Cry2) and period (Per1, Per2) genes. The rhythm-generating circuitry is functional in most cell types, including cultured fibroblasts. Using this system, we show that significant reduction in RNA polymerase II-dependent transcription did not abolish circadian oscillations, but surprisingly accelerated them. A similar period shortening was observed at reduced incubation temperatures in wild-type mouse fibroblasts, but not in cells lacking Per1. Our data suggest that mammalian circadian oscillators are resilient to large fluctuations in general transcription rates and temperature, and that PER1 has an important function in transcription and temperature compensation.
哺乳动物的昼夜节律振荡器被认为依赖于时钟基因表达中的转录/翻译反馈回路。主要且关键的回路涉及隐花色素（Cry1、Cry2）和周期（Per1、Per2）基因的自抑制。节律产生电路在大多数细胞类型中都有功能，包括培养的成纤维细胞。利用这个系统，我们表明RNA聚合酶II依赖性转录的显著降低并没有消除昼夜节律振荡，反而令人惊讶地加速了它们。在野生型小鼠成纤维细胞中，降低培养温度时观察到了类似的周期缩短现象，但在缺乏Per1的细胞中没有。我们的数据表明，哺乳动物的昼夜节律振荡器对一般转录速率和温度的大幅波动具有弹性，并且PER1在转录和温度补偿中具有重要功能。
