Department of Ecology, Evolution and Environmental Biology, Columbia University, 10th Floor Schermerhorn Extension, 1200 Amsterdam Avenue, New York, NY, USA.
Integr Comp Biol. 2019 Aug 1;59(2):264-272. doi: 10.1093/icb/icz034.
Negative feedback of the vertebrate stress response via the hypothalamic-pituitary-adrenal (HPA) axis is regulated by glucocorticoid receptors in the brain. Epigenetic modification of the glucocorticoid receptor gene (Nr3c1), including DNA methylation of the promoter region, can influence expression of these receptors, impacting behavior, physiology, and fitness. However, we still know little about the long-term effects of these modifications on fitness. To better understand these fitness effects, we must first develop a non-lethal method to assess DNA methylation in the brain that allows for multiple measurements throughout an organism's lifetime. In this study, we aimed to determine if blood is a viable biomarker for Nr3c1 DNA methylation in two brain regions (hippocampus and hypothalamus) in adult European starlings (Sturnus vulgaris). We found that DNA methylation of CpG sites in the complete Nr3c1 putative promoter varied among tissue types and was lowest in blood. Although we identified a similar cluster of correlated Nr3c1 putative promoter CpG sites within each tissue, this cluster did not show any correlation in DNA methylation among tissues. Additional studies should consider the role of the developmental environment in producing epigenetic modifications in different tissues.
脊椎动物应激反应的负反馈通过下丘脑-垂体-肾上腺（HPA）轴进行调节，其受脑内糖皮质激素受体的调控。糖皮质激素受体基因（Nr3c1）的表观遗传修饰，包括启动子区域的 DNA 甲基化，可以影响这些受体的表达，从而影响行为、生理和适应性。然而，我们对这些修饰对适应性的长期影响仍知之甚少。为了更好地了解这些适应性影响，我们必须首先开发一种非致死性方法来评估大脑中的 DNA 甲基化，从而允许在生物体的整个生命周期内进行多次测量。在这项研究中，我们旨在确定血液是否可以作为成年欧洲椋鸟（Sturnus vulgaris）两个脑区（海马体和下丘脑）中 Nr3c1 DNA 甲基化的可行生物标志物。我们发现，完整 Nr3c1 假定启动子中 CpG 位点的 DNA 甲基化在组织类型之间存在差异，在血液中最低。尽管我们在每个组织中都发现了类似的 Nr3c1 假定启动子 CpG 位点相关簇，但该簇在组织间的 DNA 甲基化中没有显示出任何相关性。其他研究应考虑发育环境在不同组织中产生表观遗传修饰的作用。
