Diurnal transcriptome atlas of a primate across major neural and peripheral tissues

Abstract

Diurnal gene expression patterns underlie time-of-the-day-specific functional specialization of tissues. However, available circadian gene expression atlases of a few organs are largely from nocturnal vertebrates. We report the diurnal transcriptome of 64 tissues, including 22 brain regions, sampled every 2 hours over 24 hours, from the primate (baboon). Genomic transcription was highly rhythmic, with up to 81.7% of protein-coding genes showing daily rhythms in expression. In addition to tissue-specific gene expression, the rhythmic transcriptome imparts another layer of functional specialization. Most ubiquitously expressed genes that participate in essential cellular functions exhibit rhythmic expression in a tissue-specific manner. The peak phases of rhythmic gene expression clustered around dawn and dusk, with a "quiescent period" during early night. Our findings also unveil a different temporal organization of central and peripheral tissues between diurnal and nocturnal animals.

Systems approach reveals photosensitivity and PER 2 level as determinants of clock‐modulator efficacy

“… The model of the intracellular mammalian circadian clock, Kim–Forger model, which was developed to accurately simulate the mouse SCN (Kim & Forger, ), was used for the new NHP model as clock gene expression profiles in the SCN of cynomolgus monkeys have not been measured. Nevertheless, due to the new light module, the NHP model simulates more advanced clock gene expression compared with the original mouse model under LD, which is consistent with the advanced clock gene expression seen in the SCN of baboons compared with that of mice under LD (Mure et al , ). The pharmacodynamic parameters, describing the intracellular action of PF‐670462 (e.g., binding of PF670 with CK1δ/ε), of the original systems chronopharmacology model (Kim et al , ), were kept as they are expected to be similar between NHPs and mice. The reduced photosensitivity due to adaptation for light during daytime is assumed to be completely recovered after nighttime if it is long enough (≥ 8 h). To simulate the phase shift of activity onsets with the model, we used the phase shift of the simulated BMAL1 gene expression profile as the phase of BMAL1 gene expression profiles and activity onset is highly correlated (Kiessling et al , ). However, as the phases of all clock gene expression profiles are tightly interlocked in the model, the result changes little even if the phase of other clock gene expression profiles is used. …”

Time zones of pancreatic islet metabolism

“…Additional challenge in translating clock studies from mouse/rat to human models is related to the peripheral clock differences of nocturnal vs. diurnal species. Whereas the circadian phase for core‐clock genes is kept between diurnal and nocturnal species at the SCN level, a phase‐shift is observed in peripheral organs, which is typically about 8 to 10 hours rather than 12 hours . The question remains at what level such a phase‐shift between nocturnal and diurnal species occurs, and why it is not precisely 12 hours in the periphery.…”

The intertwined roles of circadian rhythmsand neuronal metabolism fueling drug reward and addiction

“…Additional proteins modulate the phasing and amplitude of molecular clocks. Recent transcriptomic surveys suggest a range of 40–80% of genes within the mammalian genome are regulated in a rhythmic manner, depending on the assay methodology and species [32,33]. Core circadian genes, including Clock, Bmal1, Per2, and Cry2 , are the most consistently rhythmic genes between tissues, indicating other clock-controlled genes (CCGs) may be tissue and/or cell-type specific [27,33,34].…”