A circadian gene expression atlas in mammals assayed by microarray

To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more splice forms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy. 288 samples total covering 12 different tissues, with no replicates. Each tissue sampled every 2 hours for 2 days (24 samples per tissue).为阐明生物钟（circadian clock）在小鼠生理与行为中的调控作用，本研究采用RNA测序（RNA-seq）与DNA芯片技术，对12种小鼠器官的转录组进行了时序定量分析。研究发现，全基因组中43%的蛋白质编码基因在机体不同组织中存在转录节律性表达，且该节律大多呈现组织特异性。在多数器官中，大量节律振荡基因的表达峰值均出现在黎明与黄昏前的转录高峰时段。通过分析节律基因的基因组特征，我们发现相较于非振荡基因，节律基因呈现出成簇分布、基因长度更长、可变剪接形式更多的特点。系统级分析揭示了全身基因通路复杂且精细的节律性调控网络。此外，本研究还检测到超过1000种已知及新型非编码RNA（ncRNAs）的表达存在节律振荡。小鼠与人类间保守的非编码RNA，其节律表达比例与蛋白质编码基因相近，这一结果支持了非编码RNA在介导生物钟功能中发挥潜在作用的假说。尤为重要的是，本研究发现多数畅销药物及世界卫生组织（World Health Organization，WHO）基本药物均直接靶向节律基因的表达产物。此类药物大多半衰期较短，因此可通过时序给药方案提升临床疗效。综上，本研究揭示了哺乳动物生物钟兼具关键性、系统性与出人意料的调控功能，同时为时辰治疗学的发展提供了理论框架。本数据集总计包含288个样本，覆盖12种不同组织，且无生物学重复。每种组织每2小时采样一次，连续采样2天，单组织样本量为24个。