Epigenetics of Sleep and Chronobiology

Abstract

The circadian clock choreographs fundamental biological rhythms. This system is comprised of the master circadian pacemaker in the suprachiasmatic nucleus and associated pacemakers in other tissues that coordinate complex physiological processes and behaviors, such as sleep, feeding, and metabolism. The molecular circuitry that underlies these clocks and orchestrates circadian gene expression has been the focus of intensive investigation, and it is becoming clear that epigenetic factors are highly integrated into these networks. In this review, we draw attention to the fundamental roles played by epigenetic mechanisms in transcriptional and post-transcriptional regulation within the circadian clock system. We also highlight how alterations in epigenetic factors and mechanisms are being linked with sleep-wake disorders. These observations provide important insights into the pathogenesis and potential treatment of these disorders and implicate epigenetic deregulation in the significant but poorly understood interconnections now emerging between circadian processes and neurodegeneration, metabolic diseases, cancer, and aging.

Circulating miR-200–family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time

“…Bioinformatics tools were used to predict miRNAs presenting putative sites for circadian transcription factors in their promoters, and the diurnal variation of miR-27b in human leukocytes was experimentally validated (37). However, most of the studies demonstrating rhythmic profiles of miRNA expression are conducted in model organisms, such as mice, Drosophila, and Arabidopsis (39), and data from humans are scarce. Moreover, it seems that the same miRNA may be regulated in distinct tissues differently, because day-night rhythmicity was observed in miR-142-5p levels in vitreous humor (40) but not in blood (41).…”

Sleep and fatigue in pediatric oncology: A review of the literature

“…However, if cancer cells can disrupt these circadian oscillations and not have periods of cellular inactivity, then there is the potential for uninterrupted replication. One mechanism hypothesised to achieve this is via DNA methylation of specific clock genes, which not only impacts the peripheral circadian clocks but also the central 'master' circadian clock, potentially leading to sleep problems [24]. Furthermore, histone posttranslational modifications and chromatin remodelling have been associated with regulating circadian clock gene expression in a number of conditions and syndromes in which disrupted sleep is symptomatic [24].…”

“…One mechanism hypothesised to achieve this is via DNA methylation of specific clock genes, which not only impacts the peripheral circadian clocks but also the central 'master' circadian clock, potentially leading to sleep problems [24]. Furthermore, histone posttranslational modifications and chromatin remodelling have been associated with regulating circadian clock gene expression in a number of conditions and syndromes in which disrupted sleep is symptomatic [24]. Whether the same mechanism is involved in the disruption to the circadian rhythm and consequent sleep disorders related to cancer, is yet to be elucidated.…”

Case-control study of candidate gene methylation and adenomatous polyp formation

“…For example, cancer risk factors that can alter clock gene expression, such as shiftwork or sleep disturbances, also may exert epigenetic effects. 87–91 Global DNA hypomethylation in PBLs was recently observed among night workers relative to those working days, and among the clock genes examined, the largest differences in hypomethylation were observed within PER3 loci. 89 In the present study, neither the proportion of current shiftworkers nor those who engaged in at least one year of shiftwork differed by adenoma case status (Table 1), or by MINT1, PER1 , or PER3 methylation status (data not shown).…”