Coordination of the transcriptome and metabolome by the circadian clock
Coordination of the transcriptome and metabolome by the circadian clock
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DOI：
10.1073/pnas.1118726109
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发表时间：
2012-04-03
影响因子：
11.1
通讯作者：
Sassone-Corsi, Paolo
中科院分区：
文献类型：
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作者：
Eckel-Mahan, Kristin L.;Patel, Vishal R.;Sassone-Corsi, Paolo
生物钟通过基因组的重要部分的转录控制来管理大量的生理功能。生物钟的紊乱会导致代谢紊乱，包括肥胖和糖尿病。由于食物是外周生物钟的有效时间表（ZT），因此代谢物被认为是组织（如肝脏）的昼夜节律时间的细胞换能器。从一个全面的数据集超过500代谢物鉴定质谱，我们揭示了许多代谢物，包括那些在氨基酸和碳水化合物的代谢途径以及脂质，核苷酸和外源性代谢途径的协调时钟控制振荡。使用计算建模，我们提出的证据之间的昼夜转录组和特定的代谢途径的协同节点。这些节点的验证揭示了不同的代谢途径，包括尿嘧啶补救途径，以昼夜节律的方式和时钟依赖性的方式振荡。这个综合地图说明了昼夜代谢组，转录组和蛋白质组内的一致性，以及这些如何通过协同操作以实现代谢稳态的特定节点连接。
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.