Genome-wide circadian regulation: A unique system for computational biology

Abstract

Circadian rhythms are 24-hour oscillations affecting an organism at multiple levels from gene expression all the way to tissues and organs. They have been observed in organisms across the kingdom of life, spanning from cyanobacteria to humans. In mammals, the master circadian pacemaker is located in the hypothalamic suprachiasmatic nuclei (SCN) in the brain where it synchronizes the peripheral oscillators that exist in other tissues. This system regulates the circadian activity of a large part of the transcriptome and recent findings indicate that almost every cell in the body has this clock at the molecular level. In this review, we briefly summarize the different factors that can influence the circadian transcriptome, including light, temperature, and food intake. We then summarize recently identified general principles governing genome-scale circadian regulation, as well as future lines of research. Genome-scale circadian activity represents a fascinating study model for computational biology. For this purpose, systems biology methods are promising exploratory tools to decode the global regulatory principles of circadian regulation.

Disruption of Circadian Transcriptome in Lung by Acute Sleep Deprivation

“…In contrast, the 712 “AR-R” genes that gained circadian expression after sleep deprivation were enriched in processes, such as epithelial tube morphogenesis ( p = 7.63E-06), vasculature development ( p = 0.000375), morphogenesis of a branching structure ( p = 6.89E-05), and morphogenesis of a branching epithelium ( p = 6.89E-05; Figures 2B , C ). In addition, we observed a strong positive correlation between mean expression and amplitude (E-A correlation) of periodically expressed genes in both control and SD conditions ( R 2 > 0.75, Figure 2D ), supporting the energetic optimization models of the transcriptome in the two conditions ( Wang et al, 2015 ; Cheng et al, 2019 ; Sun et al, 2020 ). Notably, the E-A correlation in the two conditions was comparable, implicating that a similar level of optimization on the transcriptome was achieved.…”

“…In the hierarchical organization of circadian gene transcription, the hypothalamic suprachiasmatic nucleus (SCN) acts as a master pacemaker to synchronize or entrain peripheral clocks throughout the body ( Husse et al, 2015 ). Nevertheless, it is thought that proximally 5–20% of genes expressed in any particular tissue including lung undergo circadian oscillations at the mRNA level ( Sun et al, 2020 ).…”

Interrelation of Biological Rhythms and Circadian Hormones Producement and Their Impact on Medicine Usage

“…Nowadays, the majority of scientists support the multi-oscillatory concept of regulation of the circulatory system of mammals with a central oscillator in the suprachiasmatic nucleuses of hypothalamus (CNS) -«the master clock» and the main humoral modulator -pineal gland, which performs its chronobiotic function by melatonin which is a "sleep hormone" [6,7,[16][17][18][19][20][21][22]. The physiological significance of melatonin is manifested in the synchronization of different biological processes according to day-and night-time illumination as well as during season changes.…”

Gene networks under circadian control exhibit diurnal organization in primate organs

“…Rhythmic interactions refer to gene pairs that are rhythmic across time. Testing these concepts has been difficult so far because only one or a few tissues are analyzed by high-throughput sequencing technologies in any given study (Doherty and Kay 2010;Hughes et al 2017;Sun et al 2020). Still, several large-scale circadian transcriptomes have been recently reported (Zhang et al 2014;Mure et al 2018;Ruben et al 2018), making examination of this conceptual framework feasible.…”