Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex

• Published in: Nature communications Vol. 9; no. 1; pp. 1616 - 11
• Main Authors: Coulson, Rochelle L., Yasui, Dag H., Dunaway, Keith W., Laufer, Benjamin I., Vogel Ciernia, Annie, Zhu, Yihui, Mordaunt, Charles E., Totah, Theresa S., LaSalle, Janine M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24-04-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 14/32; 38; 38/71; 38/77; 45/22; 45/23; 631/208/177; 631/378/1385/2640; 692/308/1426; 692/4017; Animals; Brain; Brain - physiology; Central pattern generator; Cerebral Cortex - metabolism; Chromatin; Chromatin - genetics; Chromatin - metabolism; Circadian Rhythm; Circadian rhythms; Crosstalk; Deoxyribonucleic acid; Diurnal; DNA; DNA Methylation; Epigenetics; Female; Gene Deletion; Genes; Genomic imprinting; Humanities and Social Sciences; Humans; Male; Mice; multidisciplinary; Oscillations; Prader-Willi syndrome; Prader-Willi Syndrome - genetics; Prader-Willi Syndrome - metabolism; RNA, Small Nucleolar - genetics; RNA, Small Nucleolar - metabolism; Science; Science (multidisciplinary); Sleep
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03676-0

Rhythmic oscillations of physiological processes depend on integrating the circadian clock and diurnal environment. DNA methylation is epigenetically responsive to daily rhythms, as a subset of CpG dinucleotides in brain exhibit diurnal rhythmic methylation. Here, we show a major genetic effect on rhythmic methylation in a mouse
Snord116
deletion model of the imprinted disorder Prader–Willi syndrome (PWS). More than 23,000 diurnally rhythmic CpGs are identified in wild-type cortex, with nearly all lost or phase-shifted in PWS. Circadian dysregulation of a second imprinted
Snord
cluster at the Temple/Kagami-Ogata syndrome locus is observed at the level of methylation, transcription, and chromatin, providing mechanistic evidence of cross-talk. Genes identified by diurnal epigenetic changes in PWS mice overlapped rhythmic and PWS-specific genes in human brain and are enriched for PWS-relevant phenotypes and pathways. These results support the proposed evolutionary relationship between imprinting and sleep, and suggest possible chronotherapy in the treatment of PWS and related disorders.
Many genes have oscillating gene expression pattern in circadian centers of the brain. This study shows cortical diurnal DNA methylation oscillation in a mouse model of Prader-Willi syndrome, and describes corresponding changes in gene expression and chromatin compaction.