a Department of Medical Microbiology and Immunology , University of California , Davis , CA , USA.
b Department of Psychology , University of California , Davis , CA , USA.
Epigenetics. 2018;13(3):318-330. doi: 10.1080/15592294.2018.1451720. Epub 2018 May 10.
Augmented maternal care during the first postnatal week promotes life-long stress resilience and improved memory compared with the outcome of routine rearing conditions. Recent evidence suggests that this programming commences with altered synaptic connectivity of stress sensitive hypothalamic neurons. However, the epigenomic basis of the long-lived consequences is not well understood. Here, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to examine the effects of augmented maternal care on DNA cytosine methylation, gene expression, and miRNA expression. A total of 9,439 differentially methylated regions (DMRs) associated with augmented maternal care were identified in male offspring hypothalamus, as well as a modest but significant decrease in global DNA methylation. Differentially methylated and expressed genes were enriched for functions in neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation, as well as known stress response genes. Twenty prioritized genes were identified as highly relevant to the stress resiliency phenotype. This combined unbiased approach enabled the discovery of novel genes and gene pathways that advance our understanding of the epigenomic mechanisms underlying the effects of maternal care on the developing brain.
在产后第一周增加母婴护理可促进终生的抗压能力和改善记忆，这比常规养育条件的效果要好。最近的证据表明，这种编程始于压力敏感下丘脑神经元的突触连接改变。然而，这种长期影响的表观基因组基础还不太清楚。在这里，我们采用全基因组亚硫酸氢盐测序（WGBS）、RNA 测序（RNA-seq）和多重 microRNA（miRNA）分析，研究了增加母婴护理对雄性后代下丘脑的 DNA 胞嘧啶甲基化、基因表达和 miRNA 表达的影响。在雄性后代的下丘脑发现了 9439 个与增加母婴护理相关的差异甲基化区域（DMR），以及整体 DNA 甲基化的适度但显著降低。差异甲基化和表达的基因富集了神经递质传递、神经发育、蛋白质合成和氧化磷酸化以及已知的应激反应基因的功能。有 20 个被优先确定的基因与应激弹性表型高度相关。这种综合的无偏方法使我们能够发现新的基因和基因途径，从而加深我们对母婴护理对发育中大脑的影响的表观基因组机制的理解。
