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

摘要: Circadian rhythms modulate the biology of many human tissues, including brain and are driven by a near 24-hour transcriptional feedback loop. These paralleled large portions transcriptome. The role dynamic DNA methylation in influencing these is uncertain. While recent work Neurospora suggests that site-specific circadian may play modulating fungal molecular clock, such their relationship to RNA expression have not, our knowledge, been elucidated mammalian tissues. We hypothesized exist brain, driving expression. analyzed levels post-mortem dorsolateral prefrontal cortex samples from 738 subjects. assessed for rhythmicity 420,132 sites throughout genome considering as function clock time death parameterizing data using cosine functions. determined global statistical significance permutation. then related with sequencing. found evidence significant methylation. Regions transcription start were enriched high-amplitude rhythmic sites, which turn locked nearby genes, nadir preceding peak transcript 1-3 hours. Weak ante-mortem rest-activity associated lower amplitude older age presence Alzheimer's disease. findings support hypothesis methylation, particularly gene cortex, be affected