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.
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Authors | Rochelle L Coulson, Dag H Yasui, Keith W Dunaway, Benjamin I Laufer, Annie Vogel Ciernia, Yihui Zhu, Charles E Mordaunt, Theresa S Totah, Janine M LaSalle |
Journal | Nature communications
(Nat Commun)
Vol. 9
Issue 1
Pg. 1616
(04 24 2018)
ISSN: 2041-1723 [Electronic] England |
PMID | 29691382
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Chromatin
- RNA, Small Nucleolar
- SNORD116 RNA, human
- SNORD116 RNA, mouse
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Topics |
- Animals
- Brain
(physiology)
- Cerebral Cortex
(metabolism)
- Chromatin
(genetics, metabolism)
- Circadian Rhythm
- DNA Methylation
- Female
- Gene Deletion
- Humans
- Male
- Mice
- Prader-Willi Syndrome
(genetics, metabolism)
- RNA, Small Nucleolar
(genetics, metabolism)
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