To help understand the influence of synchronization between subordinate oscillators, we propose the concepts of “global cycling genes” and “rhythmic interactions” for analysis of the transcriptome. Although it is well known that a substantial fraction (3–16%) of transcribed mRNAs show rhythmic expression 10, 11, 12, 13, the effects of global circadian synchronization on the transcriptomes of individual organs remains elusive. These core clock genes regulate the expression of other molecules, thus generating the rhythmicity of various biological physiology. The core circadian network consists of CLOCK (along with its paralog NPAS2) and its heterodimeric partner BMAL1 (ARNTL), which bind to their downstream targets including PER1, PER2, CRY1, and CRY2 7, 8, 9. At the molecular level, circadian oscillation in mammals is regulated by the transcriptional/translational autoregulatory feedback loop (TTFL). The central clock regulates peripheral clocks slightly each day to adapt to the 24 h day-night cycle, as the intrinsic circadian period is longer than a day 6. This system is replicated in individual cells, which need to be synchronized with each other to properly perform their organ’s functions 3, 4, 5. The mammalian circadian system is hierarchical in structure, with the brain’s suprachiasmatic nucleus (SCN) acting as a master pacemaker to orchestrate clocks in other organs 1, 2, 3. 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. In addition, a majority of SARS-CoV-2-related genes and modules are rhythmically expressed, which have significant network proximities with circadian regulators. A substantial number of diseases only form significant disease modules at either daytime or nighttime. Daytime networks were enriched for genes involved in metabolism, while nighttime networks were enriched for genes associated with growth and cellular signaling. Additionally, two basic network modes were observed at the systems level: daytime and nighttime mode. We found that 53.4% (8120) of baboon genes are oscillating body-wide. Here, we utilize integrative analysis of a baboon diurnal transcriptome atlas to characterize the properties of gene networks under circadian control. While interactions between these molecular clocks are necessary for proper homeostasis, these features remain undefined. At the molecular level, this process is defined by the cyclical co-expression of both core transcription factors and their downstream targets across time. Mammalian organs are individually controlled by autonomous circadian clocks.
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