Genomic Imprinting: A New Epigenetic Perspective of Sleep Regulation
Overview A growing corpus of data indicates that epigenetic mechanisms regulate sleep and sleep-wake cycles. Here, I discuss recent evidence showing that genomic imprinting, an epigenetic mechanism that regulates parent-of-origin effects in mammals, is involved in the control of rapid eye movement (REM) sleep. REM sleep is an evolutionarily recent form of sleep that is characterized by important electrophysiological, metabolic, and thermoregulatory changes. The link between imprinting and REM
... eep offers new insights into the epigenetic mechanisms underlying sleep physiology. Sleep is associated with significant changes in the expression of many genes, which suggests that sleep regulates a number of physiological and/or behavioural functions. Approximately 15% of transcripts across the genome oscillate along sleep-wake cycles, more than 40% of protein-coding genes oscillate in at least one tissue , and a number of molecular pathways sense epigenetic changes that depend on sleep. For example, sleep loss disrupts the circadian rhythm in 20% of the oscillating genes in the brain  and affects the DNA binding of clock genes by acting on the methylation state of their promoters  . Moreover, significant methylation changes have recently been reported in mice when their sleep-wake cycles are manipulated starting in the early stages of development after birth  . There are various theories for the function of sleep. For example, one theory was proposed that the function of sleep is to decrease energy demands, while another theory suggested that sleep is to restore cellular and subcellular processes  . At the moment, a new theory proposes that a positive selective pressure for sleep is associated with the role of sleep in fundamental mechanisms that regulate the communication between neurons  and, more generally, in connectivity processes that wire the brain  . Neuronal properties are the most frequently investigated functions of sleep, and these studies indicate that sleep has a significant role in cognitive processes (e.g., memory consolidation ). Novel insights are now emerging for the epigenetic mechanisms regulating sleep. In particular, the role of genomic imprinting in sleep regulation has been systematically studied in recent years. Genomic imprinting is an epigenetic mechanism that results in the allele-specific expression of approximately 200 genes according to the parental origin and is unique to mammals among vertebrates  . Imprinted genes play a crucial role in the placenta and prenatal development and, after birth, have been demonstrated to control important metabolic and physiological functions (e.g., thermogenesis) as well as behavioural and cognitive processes [10, 11] . Imprinted genes have important roles during the perinatal period  , which is a crucial time window in development, for the formation and integration of all biological systems, including the homeostatic control of sleep and the formation of the internal (circadian) clock [12, 13] .