Fasolino Maria, Zhou Zhaolan
Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Genes (Basel). 2017 May 13;8(5):141. doi: 10.3390/genes8050141.
A neuron is unique in its ability to dynamically modify its transcriptional output in response to synaptic activity while maintaining a core gene expression program that preserves cellular identity throughout a lifetime that is longer than almost every other cell type in the body. A contributing factor to the immense adaptability of a neuron is its unique epigenetic landscape that elicits locus-specific alterations in chromatin architecture, which in turn influences gene expression. One such epigenetic modification that is sensitive to changes in synaptic activity, as well as essential for maintaining cellular identity, is DNA methylation. The focus of this article is on the importance of DNA methylation in neuronal function, summarizing recent studies on critical players in the establishment of (the "writing"), the modification or erasure of (the "editing"), and the mediation of (the "reading") DNA methylation in neurodevelopment and neuroplasticity. One "reader" of DNA methylation in particular, methyl-CpG-binding protein 2 (MeCP2), is highlighted, given its undisputed importance in neuronal function.
神经元具有独特的能力，能够响应突触活动动态改变其转录输出，同时维持一个核心基因表达程序，该程序在比体内几乎所有其他细胞类型都长的生命周期内保持细胞身份。神经元具有巨大适应性的一个促成因素是其独特的表观遗传格局，这种格局引发染色质结构的位点特异性改变，进而影响基因表达。对突触活动变化敏感且对维持细胞身份至关重要的一种表观遗传修饰是DNA甲基化。本文重点关注DNA甲基化在神经元功能中的重要性，总结了近期关于神经发育和神经可塑性中DNA甲基化的建立（“书写”）、修饰或擦除（“编辑”）以及介导（“读取”）的关键参与者的研究。鉴于其在神经元功能中无可争议的重要性，特别强调了一种DNA甲基化的“读取器”，即甲基CpG结合蛋白2（MeCP2）。
