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Nat Commun. 2018 Apr 24;9(1):1616. doi: 10.1038/s41467-018-03676-0.

Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex.

Author information

1
Medical Microbiology and Immunology, Genome Center, MIND Institute, University of California, Davis, CA, 95616, USA.
2
Medical Microbiology and Immunology, Genome Center, MIND Institute, University of California, Davis, CA, 95616, USA. jmlasalle@ucdavis.edu.

Abstract

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.

PMID:
29691382
PMCID:
PMC5915486
DOI:
10.1038/s41467-018-03676-0
[Indexed for MEDLINE]
Free PMC Article

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