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Harmonics of Circadian Gene Transcription in Mammals

机译：哺乳动物昼夜节律基因转录的谐波

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The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse.
机译：昼夜节律钟是在大多数哺乳动物组织中发现的分子和细胞振荡器，可调节节律性生理和行为。许多研究已经探讨了昼夜节律对细胞，器官和机体生理的贡献。我们最近开发了一种方法，可以使用高密度时间采样以前所未有的精度和准确性来观察转录振荡。在这里，我们报告了从小鼠肝脏，NIH3T3和U2OS细胞振荡转录的比较。这项研究得出了一些令人惊讶的发现，其中包括振荡器的自主细胞模型与从完整小鼠中收获的组织相比，循环转录物数量的100倍差异。令人惊讶的是，我们发现了两个基因簇，它们在肝脏中以昼夜节律的第二次和第三次谐波循环，而没有在培养的细胞中循环。验证实验表明，12小时的振荡转录本还出现在其他几种周围组织中，包括心脏，肾脏和肺部。这些谐波会在体外以及受限制的进食条件下丢失。综上所述，这些研究说明了时间采样对多重测试的重要性，建议在使用自主细胞模型研究时钟输出时要谨慎，并证明小鼠中昼夜节律基因表达的谐波。

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