Thomas Elizabeth A
Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, United States.
Neurosci Lett. 2016 Jun 20;625:34-9. doi: 10.1016/j.neulet.2015.10.060. Epub 2015 Nov 11.
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.
亨廷顿舞蹈症（HD）是一种由HTT基因中的CAG重复突变引起的毁灭性神经退行性疾病。越来越多的证据表明，表观遗传修饰在HD发病机制中起关键作用。疾病蛋白亨廷顿蛋白的表达，由于组蛋白修饰复合物的破坏以及与染色质相关因子相互作用的改变，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，现在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甲基化是一种已被深入研究的表观遗传修饰，然而，它在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，还将在相关环境因素及其与HD的潜在联系的背景下讨论跨代表观遗传遗传。HD表观遗传状态的研究为深入了解与HD相关的风险因素和致病机制以及为治疗选择提供信息提供了机会。
