Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex
Rochelle L. Coulson, Dag H. Yasui, Keith Dunaway, Benjamin I. Laufer, Annie Vogel Ciernia, Charles E. Mordaunt, Theresa S. Totah, Janine M. LaSalle
Received: 12th September 17
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). Of the >23,000 diurnally rhythmic CpGs identified in wild-type cortex, 97% lost rhythmic methylation in PWS cortex. 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 obesity 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.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.