TY - JOUR
T1 - Snord116-dependent diurnal rhythm of DNA methylation in mouse cortex
AU - Coulson, Rochelle L.
AU - Yasui, Dag H.
AU - Dunaway, Keith W.
AU - Laufer, Benjamin I.
AU - Vogel Ciernia, Annie
AU - Zhu, Yihui
AU - Mordaunt, Charles E.
AU - Totah, Theresa S.
AU - Lasalle, Janine M.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045963040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045963040&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03676-0
DO - 10.1038/s41467-018-03676-0
M3 - Article
C2 - 29691382
AN - SCOPUS:85045963040
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1616
ER -