Broad epigenetic signature of maternal care in the brain of adult rats (expression)

Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, epigenetic changes at a single gene promoter are unlikely to account for the range of responses to the early life environment and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Here we show that natural variations in maternal care are associated with coordinate changes in DNA methylation, chromatin, and gene expression spanning over a hundred kilobase pairs in the hippocampus of adult rats. The offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends and higher transcriptional activity across many genes, suggesting that a broad epigenetic regulation of gene expression may form part of a coordinated response to early maternal care.母性行为与大鼠及人类海马体中行为模式及NR3C1（糖皮质激素受体）基因的表观遗传编程存在显著关联。然而，单一基因启动子的表观遗传改变，难以解释早期生命环境所引发的各类应答，以及成年大鼠因母性行为差异而出现的数百个其他基因表达的持续变化。本研究发现，母性行为的自然变异与成年大鼠海马体中跨越逾100千碱基对区域的DNA甲基化（DNA methylation）、染色质（chromatin）及基因表达的协同改变密切相关。相较于低母性行为水平母鼠的子代，高母性行为水平母鼠的子代在启动子（promoter）、外显子（exon）及基因末端均出现表观遗传改变，且众多基因的转录活性更高，这表明基因表达的广泛表观遗传调控或为早期母性行为协同应答的组成部分。