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24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex


Circadian rhythms are intrinsic 24-hour biological rhythms that influence many aspects of human biology, including normal and abnormal human brain functions such as cognition and seizures. Circadian rhythms are maintained by a near 24-hour feedback loop mediated by a series of “clock” genes that are similar across species, including humans. However, the specific mechanisms underlying the circadian regulation of gene transcription are unknown. DNA methylation is an epigenetic mechanism that can influence gene expression without changes in DNA sequence. The 24-hour rhythms of DNA methylation are one mechanism contributing to 24-hour rhythms of clock gene expression in fungi. However, this has not been demonstrated in mammals including humans. In this study, we examined levels of DNA methylation at>400,000 sites across the genome in the brains of 738 human subjects and showed significant 24-hour rhythms of DNA methylation. Moreover, we showed that for specific locations of DNA methylation site, these rhythms of methylation were linked to rhythms of gene expression. This is important because it suggests that circadian rhythms of DNA methylation may be an important mechanism underlying circadian rhythms of gene expression in the human brain, and hence circadian rhythms of normal and abnormal brain function.


Vyšlo v časopise: 24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004792
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004792

Souhrn

Circadian rhythms are intrinsic 24-hour biological rhythms that influence many aspects of human biology, including normal and abnormal human brain functions such as cognition and seizures. Circadian rhythms are maintained by a near 24-hour feedback loop mediated by a series of “clock” genes that are similar across species, including humans. However, the specific mechanisms underlying the circadian regulation of gene transcription are unknown. DNA methylation is an epigenetic mechanism that can influence gene expression without changes in DNA sequence. The 24-hour rhythms of DNA methylation are one mechanism contributing to 24-hour rhythms of clock gene expression in fungi. However, this has not been demonstrated in mammals including humans. In this study, we examined levels of DNA methylation at>400,000 sites across the genome in the brains of 738 human subjects and showed significant 24-hour rhythms of DNA methylation. Moreover, we showed that for specific locations of DNA methylation site, these rhythms of methylation were linked to rhythms of gene expression. This is important because it suggests that circadian rhythms of DNA methylation may be an important mechanism underlying circadian rhythms of gene expression in the human brain, and hence circadian rhythms of normal and abnormal brain function.


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Genetika Reprodukčná medicína

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