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昼夜节律控制下的基因网络在灵长类器官中表现出昼夜组织。

Gene networks under circadian control exhibit diurnal organization in primate organs.

机构信息

CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Max Planck Institute of Psychiatry, Proteomics and Biomarkers, Munich, 80804, Germany.

出版信息

Commun Biol. 2022 Jul 29;5(1):764. doi: 10.1038/s42003-022-03722-0.

Abstract

Mammalian organs are individually controlled by autonomous circadian clocks. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and their downstream targets across time. While interactions between these molecular clocks are necessary for proper homeostasis, these features remain undefined. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. We found that 53.4% (8120) of baboon genes are oscillating body-wide. Additionally, two basic network modes were observed at the systems level: daytime and nighttime mode. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. A substantial number of diseases only form significant disease modules at either daytime or nighttime. In addition, a majority of SARS-CoV-2-related genes and modules are rhythmically expressed, which have significant network proximities with circadian regulators. Our data suggest that synchronization amongst circadian gene networks is necessary for proper homeostatic functions and circadian regulators have close interactions with SARS-CoV-2 infection.

摘要

哺乳动物器官由自主的生物钟单独控制。在分子水平上,这个过程是由核心转录因子及其下游靶基因在时间上的周期性共表达定义的。虽然这些分子钟之间的相互作用对于正常的体内平衡是必要的,但这些特征仍然没有定义。在这里,我们利用狨猴昼夜转录组图谱的综合分析来描述受生物钟控制的基因网络的特性。我们发现,53.4%(8120 个)的狨猴基因在全身范围内呈周期性波动。此外,在系统水平上观察到两种基本的网络模式:白天模式和夜间模式。白天网络富含与代谢相关的基因,而夜间网络富含与生长和细胞信号相关的基因。大量疾病仅在白天或夜间形成显著的疾病模块。此外,大多数与 SARS-CoV-2 相关的基因和模块呈节律性表达,它们与生物钟调节剂具有显著的网络接近性。我们的数据表明,生物钟基因网络的同步对于正常的体内平衡功能是必要的,并且生物钟调节剂与 SARS-CoV-2 感染有密切的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccef/9338065/1bc3fc2608d0/42003_2022_3722_Fig1_HTML.jpg

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