DNA Methylation in Huntington's Disease.
DNA Methylation in Huntington's Disease.
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DOI：
10.3390/ijms222312736
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发表时间：
2021-11-25
影响因子：
5.6
通讯作者：
Bodai L
中科院分区：
文献类型：
--
作者：
Zsindely N;Siági F;Bodai L
胞嘧啶甲基化是哺乳动物细胞中最主要的DNA修饰，是表观遗传标记的重要组成部分。这种修饰一方面是可逆的，而另一方面，可以通过连续几轮的复制来维持，在基因调控、基因组维持、跨代表观遗传和印记中发挥作用。DNA甲基化的紊乱导致了从单基因疾病到散发性代谢疾病或癌症的一系列人类疾病。DNA甲基化也被证明会影响几种神经退行性疾病，包括亨廷顿病（HD），一种致命的单基因遗传性疾病。HD是由亨廷顿蛋白中的多聚谷氨酰胺重复扩增引起的，其引起影响几种细胞过程的多方面发病机制。过去十年的研究发现，HD发病机制中复杂的全基因组DNA甲基化变化调节转录活性和基因组稳定性。本文综述了目前的证据，揭示了DNA甲基化在HD中的作用。
Methylation of cytosine in CpG dinucleotides is the major DNA modification in mammalian cells that is a key component of stable epigenetic marks. This modification, which on the one hand is reversible, while on the other hand, can be maintained through successive rounds of replication plays roles in gene regulation, genome maintenance, transgenerational epigenetic inheritance, and imprinting. Disturbed DNA methylation contributes to a wide array of human diseases from single-gene disorders to sporadic metabolic diseases or cancer. DNA methylation was also shown to affect several neurodegenerative disorders, including Huntington’s disease (HD), a fatal, monogenic inherited disease. HD is caused by a polyglutamine repeat expansion in the Huntingtin protein that brings about a multifaceted pathogenesis affecting several cellular processes. Research of the last decade found complex, genome-wide DNA methylation changes in HD pathogenesis that modulate transcriptional activity and genome stability. This article reviews current evidence that sheds light on the role of DNA methylation in HD.