Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood

Nov 4, 2015Journal of biological rhythms

Daily and Internal Clock Patterns of Gene Activity in Human Blood

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Abstract

Significant rhythmic expression was observed for 4 candidate clock-controlled genes in human blood during sleep and constant routine studies.

Rhythmic expression was confirmed for STAT3, SREBF1, TRIB1, and THRA1 in both sleep/sleep deprivation and constant routine studies.
MKNK2 exhibited rhythmic expression only in the sleep/sleep deprivation study, suggesting its regulation may be influenced by external factors.
Circadian expression was validated for PER1, PER3, and REV-ERBα in constant routine samples, while BMAL1 and HSPA1B did not show significant rhythmicity.
The findings indicate that gene expression patterns in human blood are partly regulated by both internal biological clocks and external influences like sleep and fasting.

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The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings.

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Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood

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