Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex
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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. A major genetic effect on rhythmic methylation was identified in a mouse Snord116 deletion model of the imprinted disorder Prader-Willi syndrome (PWS). > 23,000 diurnally rhythmic CpGs were 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 was 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 were 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.
ORGANISM(S): Mus musculus
PROVIDER: GSE103249 | GEO | 2018/02/27
REPOSITORIES: GEO
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