Circadian gene expression is resilient to large fluctuations in overall transcription rates
Circadian gene expression is resilient to large fluctuations in overall transcription rates
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DOI：
10.1038/emboj.2008.262
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发表时间：
2009-01-21
期刊：
影响因子：
11.4
通讯作者：
Schibler, Ueli
中科院分区：
文献类型：
--
作者：
Dibner, Charna;Sage, Daniel;Schibler, Ueli
哺乳动物昼夜节律振荡器被认为依赖于时钟基因表达中的转录/翻译反馈环。主要的和必要的环涉及隐花色素（Cry 1，Cry 2）和周期（Per 1，Per 2）基因的自抑制。节律产生电路在大多数细胞类型中起作用，包括培养的成纤维细胞。使用这个系统，我们表明，RNA聚合酶II依赖的转录显着减少并没有废除昼夜节律振荡，但令人惊讶地加速它们。在野生型小鼠成纤维细胞中，在降低的孵育温度下观察到类似的时间缩短，但在缺乏Per 1的细胞中没有观察到。我们的数据表明，哺乳动物的昼夜节律振荡器是弹性的大的波动，一般的转录速率和温度，PER 1在转录和温度补偿有一个重要的功能。
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.