Epigenetics and epigenomic medicine encompass a new science of brain and behavior that are already providing unique insights into the mechanisms underlying brain development, evolution, neuronal and network plasticity and homeostasis, senescence, the etiology of diverse neurological diseases and neural regenerative processes. Epigenetic mechanisms include DNA methylation, histone modifications, nucleosome repositioning, higher order chromatin remodeling, non-coding RNAs, and RNA and DNA editing. RNA is centrally involved in directing these processes, implying that the transcriptional state of the cell is the primary determinant of epigenetic memory. This transcriptional state can be modified not only by internal and external cues affecting gene expression and post-transcriptional processing, but also by RNA and DNA editing through activity-dependent intracellular transport and modulation of RNAs and RNA regulatory supercomplexes, and through trans-neuronal and systemic trafficking of functional RNA subclasses. These integrated processes promote dynamic reorganization of nuclear architecture and the genomic landscape to modulate functional gene and neural networks with complex temporal and spatial trajectories. Epigenetics represents the long sought after molecular interface mediating gene-environmental interactions during critical periods throughout the lifecycle. The discipline of environmental epigenomics has begun to identify combinatorial profiles of environmental stressors modulating the latency, initiation and progression of specific neurological disorders, and more selective disease biomarkers and graded molecular responses to emerging therapeutic interventions. Pharmacoepigenomic therapies will promote accelerated recovery of impaired and seemingly irrevocably lost cognitive, behavioral, sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cell fate decisions, targeted tissue remodeling and restoration of neural network integrity, plasticity and connectivity.

中文翻译：

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神经系统在健康和疾病中起作用的表观遗传原理和机制。

表观遗传学和表观基因组医学涵盖了关于脑和行为的一门新科学，已经对脑发育，进化，神经元和网络可塑性，体内平衡，衰老，各种神经系统疾病的病因和神经再生过程提供了独特的见解。表观遗传机制包括DNA甲基化，组蛋白修饰，核小体重定位，高级染色质重塑，非编码RNA以及RNA和DNA编辑。RNA主要参与指导这些过程，这意味着细胞的转录状态是表观遗传记忆的主要决定因素。这种转录状态不仅可以通过影响基因表达和转录后加工的内部和外部提示进行修饰，而且还可以通过RNA和DNA编辑，包括活性依赖的细胞内转运和RNA和RNA调节超复合物的调节，以及功能性RNA亚类的跨神经元和系统性转运。这些整合的过程促进了核结构和基因组格局的动态重组，以调节具有复杂的时空轨迹的功能基因和神经网络。表观遗传学代表了在整个生命周期的关键时期内介导基因-环境相互作用的分子接口的长期追求。环境表观基因组学的学科已开始确定环境应激源的组合概况，以调节特定神经系统疾病的潜伏期，引发和进展，以及更具选择性的疾病生物标记和对新兴治疗干预的分级分子反应。药物基因组学疗法将通过内源性区域神经干细胞命运决定的表观遗传重编程，靶向组织重塑以及神经网络完整性，可塑性和连通性的恢复，促进受损和看似不可挽回的认知，行为，感觉运动功能的加速恢复。