Harmonics of circadian gene transcription in mammals.
Harmonics of circadian gene transcription in mammals.
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DOI：
10.1371/journal.pgen.1000442
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发表时间：
2009-04
期刊：
影响因子：
4.5
通讯作者：
Hogenesch JB
中科院分区：
文献类型：
--
作者：
Hughes ME;DiTacchio L;Hayes KR;Vollmers C;Pulivarthy S;Baggs JE;Panda S;Hogenesch JB
生物钟是在大多数哺乳动物组织中发现的分子和细胞振荡器，其调节节律性生理和行为。许多研究已经解决了昼夜节律对细胞、器官和生物体生理学的贡献。我们最近开发了一种方法，使用高密度时间采样以前所未有的精度和准确度来观察转录振荡。在这里，我们报告了小鼠肝脏、NIH 3 T3和U2 OS细胞振荡转录的比较。这项研究产生了几个令人惊讶的观察结果，包括振荡器的自主细胞模型与从完整小鼠收获的组织中的循环转录本数量的100倍差异。引人注目的是，我们在肝脏中发现了两组基因，它们以昼夜节律的第二和第三谐波进行循环，但在培养的细胞中却没有。验证实验表明，12小时振荡转录本也发生在其他几个外周组织中，包括心脏，肾脏和肺。这些谐波在体外以及在受限的馈电条件下损失。总之，这些研究说明了时间采样的重要性，相对于多个测试，建议谨慎使用自主细胞模型来研究时钟输出，并证明存在的谐波的昼夜节律基因表达的小鼠。昼夜节律通过允许生物体预测其环境中的每日变化而赋予适应性优势。在过去的几年里，许多研究小组已经使用微阵列技术来系统地识别昼夜节律调节下的基因。我们已经扩展了这些研究，通过分析小鼠肝脏和两个永生化细胞系的昼夜节律转录组，以前所未有的高时间分辨率。我们在小鼠肝脏中发现了超过3,000种不同的转录本，其周期长度约为24小时。令我们惊讶的是，我们还发现了两类周期长度为12小时和8小时的基因;即，生物钟的谐波。重要的是，我们能够在其他五种组织类型中识别谐波;然而，这些节奏在分离的细胞中无法检测到。此外，当小鼠受到限制喂养时，谐波在肝脏中丢失，这表明昼夜节律谐波的至少一个分量是由喂养驱动的。
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. Circadian rhythms confer adaptive advantages by allowing organisms to anticipate daily changes in their environment. Over the last few years, many groups have used microarray technology to systematically identify genes under circadian regulation. We have extended on these studies by profiling the circadian transcriptome from the mouse liver and two immortalized cell lines at an unprecedentedly high temporal resolution. We identified over 3,000 different transcripts in the mouse liver that cycle with a period length of approximately 24 hours. To our surprise, we also identified two classes of genes which cycle with period lengths of 12 and 8 hours; i.e., harmonics of the circadian clock. Importantly, we were able to identify harmonics in five other tissue types; however, these rhythms were undetectable in disassociated cells. Moreover, harmonics were lost in the liver when mice are subjected to restricted feeding, suggesting that at least one component of circadian harmonics is driven by feeding.
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