Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques

作者：Maggie Baker, Stephen G. Lindell, Carlos A. Driscoll, Zhifeng Zhou, Qiaoping Yuan, Melanie L. Schwandt, Isaac Miller-Crews, Elizabeth A. Simpson, Annika Paukner, Pier Francesco Ferrari, Ravi Kumar, Muslima S. Razaqyar, Wolfgang H. Sommer, Juan F. López, Robert C. Thompson, David Goldman, Markus Heilig, J. Dee Higley, Stephen J. Suomi, Christina S. Barr · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1706206114 · 被引用次数：73 · 研究领域：Neuroendocrine regulation and behavior、Child and Adolescent Psychosocial and Emotional Development、Attachment and Relationship Dynamics

Significance Epigenetically programmed stress adaptation may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing to examine effects of early environment on epigenetic regulation using hippocampal samples from macaques exposed to disruption in maternal care. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene ( OXTR ), for which we observed a corresponding decrease in RNA expression. Post hoc analysis showed that a gain-of-function OXTR SNP rescued behavioral differences in early stress-exposed subjects. Our data suggest that epigenetic down-modulation of OXTR in brain could contribute to behavioral differences observed in early stress-exposed subjects and that functional genetic variation plays a role. These could have translational implications for human psychiatric disease and personality disorders.