Department of Neurology, 2nd Xiangya Hospital, Central South University, No 139, Renmin Road, Changsha, Hunan Province, China.
Hum Genomics. 2018 Jun 22;12(1):31. doi: 10.1186/s40246-018-0163-5.
Epigenetics defines the persistent modifications of gene expression in a manner that does not involve the corresponding alterations in DNA sequences. It includes modifications of DNA nucleotides, nucleosomal remodeling, and post-translational modifications (PTMs). It is becoming evident that PTMs which act singly or in combination to form "histone codes" orchestrate the chromatin structure and dynamic functions. PTMs of histone tails have been demonstrated to influence numerous biological developments, as well as disease onset and progression. Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disease of the central nervous system, of which the precise pathophysiological mechanisms remain to be fully elucidated. There is a wealth of emerging evidence that epigenetic modifications may confer risk for MS, which provides new insights into MS. Histone PTMs, one of the key events that regulate gene activation, seem to play a prominent role in the epigenetic mechanism of MS. In this review, we summarize recent studies in our understanding of the epigenetic language encompassing histone, with special emphasis on histone acetylation and histone lysine methylation, two of the best characterized histone modifications. We also discuss how the current studies address histone acetylation and histone lysine methylation influencing pathophysiology of MS and how future studies could be designed to establish optimized therapeutic strategies for MS.
表观遗传学定义了基因表达的持久修饰方式，这种修饰方式不涉及相应的 DNA 序列改变。它包括 DNA 核苷酸的修饰、核小体重塑和翻译后修饰（PTMs）。越来越明显的是，单独或组合作用形成“组蛋白密码”的 PTM 调节染色质结构和动态功能。组蛋白尾部的 PTM 已被证明会影响许多生物学发育以及疾病的发生和进展。多发性硬化症（MS）是一种中枢神经系统的自身免疫性炎症脱髓鞘和神经退行性疾病，其确切的病理生理机制仍有待充分阐明。有大量新出现的证据表明，表观遗传修饰可能会增加 MS 的风险，这为 MS 提供了新的见解。组蛋白 PTM 是调节基因激活的关键事件之一，似乎在 MS 的表观遗传机制中发挥着重要作用。在这篇综述中，我们总结了我们对包含组蛋白在内的表观遗传语言的最新研究理解，特别强调了组蛋白乙酰化和组蛋白赖氨酸甲基化，这两种组蛋白修饰是研究最充分的两种。我们还讨论了当前的研究如何解决组蛋白乙酰化和组蛋白赖氨酸甲基化对 MS 病理生理学的影响，以及未来的研究如何设计出优化 MS 的治疗策略。
