Department of Anatomy & Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Department of Systems Pharmacology and Translational Therapeutics, The University of Pennsylvania, Philadelphia, PA, USA.
Methods Mol Biol. 2024;2842:129-152. doi: 10.1007/978-1-0716-4051-7_6.
Epigenetic regulation is intrinsic to basic neurobiological function as well as neurological disease. Regulation of chromatin-modifying enzymes in the brain is critical during both development and adulthood and in response to external stimuli. Biochemical studies are complemented by numerous next-generation sequencing (NGS) studies that quantify global changes in gene expression, chromatin accessibility, histone and DNA modifications in neurons and glial cells. Neuroepigenetic editing tools are essential to distinguish between the mere presence and functional relevance of histone and DNA modifications to gene transcription in the brain and animal behavior. This review discusses current advances in neuroepigenetic editing, highlighting methodological considerations pertinent to neuroscience, such as delivery methods and the spatiotemporal specificity of editing and it demonstrates the enormous potential of epigenetic editing for basic neurobiological research and therapeutic application.
表观遗传调控是神经生物学基础功能以及神经疾病的内在特征。在大脑的发育和成年阶段，以及对外部刺激的反应过程中，染色质修饰酶的调控至关重要。生化研究补充了大量的下一代测序（NGS）研究，这些研究量化了神经元和神经胶质细胞中基因表达、染色质可及性、组蛋白和 DNA 修饰的全局变化。神经表观遗传编辑工具对于区分组蛋白和 DNA 修饰在大脑基因转录和动物行为中的存在和功能相关性至关重要。本文综述了神经表观遗传编辑的最新进展，重点介绍了与神经科学相关的方法学考虑因素，如递药方法和编辑的时空特异性，并展示了表观遗传编辑在基础神经生物学研究和治疗应用方面的巨大潜力。
