title: Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.
abstract: 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.
authors.affiliation: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Karolina
authors.initials: K
authors.lastname: Lech
authors.affiliation: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands EaStCHEM School of Chemistry, Biomedical Sciences Research Complex and Centre of Magnetic Resonance, University of St Andrews, St Andrews, United Kingdom.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ackermann
authors.affiliation: Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Revell
authors.affiliation: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands CNAG-CRG, Centro Nacional de Análisis Genómico, Parc Científic de Barcelona-Torre I, Barcelona, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Lao
authors.affiliation: Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Skene
authors.affiliation: Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands m.kayser@erasmusmc.nl.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser
mesh_terms: D000293:Adolescent; D000328:Adult; D056926:CLOCK Proteins / Q000097:blood* / Q000235:genetics*; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics*; D005215:Fasting / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008550:Melatonin / Q000097:blood; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012890:Sleep; D012892:Sleep Deprivation / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D056926:CLOCK Proteins; C486342:MKNK2 protein, human; D017346:Protein Serine-Threonine Kinases; D008550:Melatonin
keywords: clock-controlled genes; constant routine; gene expression; human blood; sleep deprivation