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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Coordination of the transcriptome and metabolome by the circadian clock
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Coordination of the transcriptome and metabolome by the circadian clock

机译：昼夜节律时钟对转录组和代谢组的协调

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摘要

The circadian clock governs a large array of physiological functions through the transcriptional control of a significant fraction of the genome. Disruption of the clock leads to metabolic disorders, including obesity and diabetes. As food is a potent zeitgeber (ZT) for peripheral clocks, metabolites are implicated as cellular transducers of circadian time for tissues such as the liver. From a comprehensive dataset of over 500 metabolites identified by mass spectrometry, we reveal the coordinate clock-controlled oscillation of many metabolites, including those within the amino acid and carbohydrate metabolic pathways as well as the lipid, nucleotide, and xenobiotic metabolic pathways. Using computational modeling, we present evidence of synergistic nodes between the circadian transcriptome and specific metabolic pathways. Validation of these nodes reveals that diverse metabolic pathways, including the uracil salvage pathway, oscillate in a circadian fashion and in a CLOCK-dependent manner. This integrated map illustrates the coherence within the circadian metabolome, transcriptome, and proteome and how these are connected through specific nodes that operate in concert to achieve metabolic homeostasis.
机译：昼夜节律时钟通过基因组很大一部分的转录控制来控制多种生理功能。时钟中断会导致代谢异常，包括肥胖症和糖尿病。由于食物是用于外围时钟的有效Zeitgeber（ZT），因此代谢产物被认为是昼夜时间对诸如肝脏等组织的细胞转化。通过质谱鉴定的500多种代谢物的综合数据集，我们揭示了许多代谢物的协调时钟控制振荡，包括氨基酸和碳水化合物代谢途径以及脂质，核苷酸和异源代谢途径中的那些。使用计算模型，我们提出了昼夜节律转录组和特定的代谢途径之间的协同节点的证据。这些节点的验证表明，包括尿嘧啶抢救途径在内的多种代谢途径以昼夜节律的方式且以时钟依赖性方式振荡。该综合图说明了昼夜节律代谢组，转录组和蛋白质组内的一致性，以及它们如何通过特定的节点相互连接以实现代谢稳态。

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  • 作者

    Kristin L. Eckel-Mahan; Vishal R. Patel; Robert P. Mohney; Katie S. Vignola; Pierre Baldt; Paolo Sassone-Corsi;

  • 作者单位

    Department of Biological Chemistry, Center for Epigenetics and Metabolism and Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697;

    Department of Computer Science, Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697;

    Metabolon, Inc., Research Triangle Park, Durham, NC 27713;

    Metabolon, Inc., Research Triangle Park, Durham, NC 27713;

    Department of Computer Science, Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697;

    Department of Biological Chemistry, Center for Epigenetics and Metabolism and Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    metabolism; diurnal; CircadiOmics; hepatic;

    机译：代谢;昼间CircadiOmics;肝的;

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