Early nurture epigenetically tunes the oxytocin receptor

•4 CpG sites in the Oxtr promoter region are homologous in humans and prairie voles.•Low levels of early parenting lead to high Oxtr DNA methylation in brain and blood.•High Oxtr methylation is associated with low Oxtr gene expression.•Low levels of early care lead to low OXTR density, likely via hi...

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Vydané v:Psychoneuroendocrinology Ročník 99; s. 128 - 136
Hlavní autori: Perkeybile, Allison M., Carter, C. Sue, Wroblewski, Kelly L., Puglia, Meghan H., Kenkel, William M., Lillard, Travis S., Karaoli, Themistoclis, Gregory, Simon G., Mohammadi, Niaz, Epstein, Larissa, Bales, Karen L., Connelly, Jessica J.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England Elsevier Ltd 01.01.2019
Predmet:
Animals
Arvicolinae
Brain - metabolism
CpG Islands - genetics
DNA methylation
DNA Methylation - genetics
Female
Male
Maternal Behavior - physiology
Maternal Behavior - psychology
Mothers - psychology
Nucleus Accumbens - metabolism
OXTR
Oxytocin
Oxytocin - metabolism
Pair Bond
Prairie vole
Promoter Regions, Genetic - genetics
Receptors, Oxytocin - genetics
Receptors, Oxytocin - physiology
Social Behavior
DNA methylation
OXTR
Social behavior
Oxytocin
Prairie vole
ISSN:0306-4530, 1873-3360, 1873-3360
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Shrnutí:•4 CpG sites in the Oxtr promoter region are homologous in humans and prairie voles.•Low levels of early parenting lead to high Oxtr DNA methylation in brain and blood.•High Oxtr methylation is associated with low Oxtr gene expression.•Low levels of early care lead to low OXTR density, likely via high Oxtr methylation.•Peripheral measures of Oxtr DNA methylation predict central levels. Mammalian sociality is regulated in part by the neuropeptide oxytocin. In prairie voles, subtle variation in early life experience changes oxytocin receptor-mediated social behaviors. We report that low levels of early care in voles leads to de novo DNA methylation at specific regulatory sites in the oxytocin receptor gene (Oxtr), impacting gene expression and protein distribution in the nucleus accumbens. DNA methylation state of the blood predicts expression in the brain indicating the utility of the blood as a biomarker for the transcription state of the brain. These experience-sensitive CpG sites are conserved in humans, are related to gene expression in the brain, and have been associated with psychiatric disorders and individual differences in neural response to social stimuli. These results identify a mechanism by which early care regulates later displays of typical prairie vole social behavior and suggest the potential for nurture driven epigenetic tuning of OXTR in humans.
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A.M.P., C.S.C., K.L.B., and J.J.C. were responsible for designing research. A.M.P., W.M.K., T.S.L., T.K., N.M., and L.E. conducted the studies. A.M.P., M.H.P., C.S.C., K.L.B., and J.J.C. analyzed and interpreted the data collected. A.M.P., C.S.C., K.L.W., S.G.G., K.L.B., and J.J.C. wrote the manuscript. All authors have approved of the final submission of this manuscript.
Author Contributions
ISSN:0306-4530
1873-3360
1873-3360
DOI:10.1016/j.psyneuen.2018.08.037