Massart R, Suderman M, Provencal N, Yi C, Bennett A J, Suomi S, Szyf M
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada; Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada; Research Unit on Children's Psycho-Social Maladjustment and St-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec H3T 1C5, Canada.
Neuroscience. 2014 May 30;268:139-48. doi: 10.1016/j.neuroscience.2014.03.021. Epub 2014 Mar 19.
5-Hydroxymethylcytosine (5hmC) is abundant in the brain, suggesting an important role in epigenetic control of neuronal functions. In this paper, we show that 5hmC and 5-methylcytosine (5mC) levels are coordinately distributed in gene promoters of the rhesus macaque prefrontal cortex. Although promoter hydroxymethylation and methylation are overall negatively correlated with expression, a subset of highly expressed genes involved in specific cerebral functions is associated with high levels of 5mC and 5hmC. These relationships were also observed in the mouse cortex. Furthermore, we found that early-life maternal deprivation is associated, in the adult monkey cortex, with DNA hydroxymethylation changes of promoters of genes related to neurological functions and psychological disorders. These results reveal that early social adversity triggers variations in brain DNA hydroxymethylation that could be detected in adulthood.
5-羟甲基胞嘧啶（5hmC）在大脑中含量丰富，这表明其在神经元功能的表观遗传控制中发挥着重要作用。在本文中，我们发现5hmC和5-甲基胞嘧啶（5mC）水平在恒河猴前额叶皮质的基因启动子中呈协同分布。尽管启动子羟甲基化和甲基化总体上与基因表达呈负相关，但参与特定脑功能的一组高表达基因与高水平的5mC和5hmC相关。在小鼠皮质中也观察到了这些关系。此外，我们发现成年猴子皮质中，早年母体剥夺与神经功能和心理障碍相关基因启动子的DNA羟甲基化变化有关。这些结果表明，早期社会逆境会引发大脑DNA羟甲基化的变化，而这种变化在成年期仍可被检测到。
