DNA methylation in Huntington's disease: Implications for transgenerational effects.
DNA methylation in Huntington's disease: Implications for transgenerational effects.
复制标题
DOI：
10.1016/j.neulet.2015.10.060
复制
发表时间：
2016-06-20
影响因子：
2.5
通讯作者：
Thomas EA
中科院分区：
文献类型：
--
作者：
Thomas EA
亨廷顿舞蹈症 (HD) 是一种毁灭性的神经退行性疾病，由 HTT 基因中的 CAG 重复突变引起。越来越多的证据表明表观遗传修饰在 HD 发病机制中发挥着关键作用。由于组蛋白修饰复合物的破坏以及与染色质相关因子的相互作用的改变，疾病蛋白亨廷顿蛋白的表达导致广泛的转录失调。这种表观遗传机制也很容易对环境因素做出反应，目前认为环境因素会影响包括 HD 在内的神经退行性疾病的风险、发病和进展。 DNA 甲基化是一种表观遗传修饰，已被深入研究，但其在 HD 中的作用才刚刚显现。在这篇综述中，将总结与 HD 相关的 DNA 甲基化差异，以及环境因素以可能改变疾病表型的方式改变 DNA 甲基化的作用。此外，跨代表观遗传将在相关环境因素及其与 HD 的潜在联系的背景下进行讨论。对 HD 的表观遗传状态的研究提供了一个机会，可以对 HD 相关的危险因素和致病机制有新的见解，并为治疗方案提供信息。
Huntington’s disease (HD) is a devastating, neurodegenerative disorder caused by a CAG repeat mutation in the HTT gene. A growing body of evidence suggests that epigenetic modifications play a key role in HD pathogenesis. Expression of the disease protein, huntingtin, leads to extensive transcriptional dysregulation due to disruption of histone-modifying complexes and altered interactions with chromatin-related factors. Such epigenetic mechanisms also readily respond to environmental factors, which are now thought to influence the risk, onset and progression of neurodegenerative disorders, including HD. DNA methylation is an epigenetic modification that has been studied intensively, however, its role in HD is just emerging. In this review, DNA methylation differences associated with HD will be summarized, as well as the role of environmental factors to alter DNA methylation in a manner that could alter disease phenotypes. Further, transgenerational epigenetic inheritance will be discussed in the context of relevant environmental factors and their potential links to HD. The study of epigenetic states in HD presents an opportunity to gain new insights into risk factors and pathogenic mechanisms associated with HD, as well as to inform about treatment options.