The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases.
The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases.
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DOI：
10.3389/fnins.2014.00397
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发表时间：
2014
影响因子：
4.3
通讯作者：
Pook MA
中科院分区：
文献类型：
--
作者：
Al-Mahdawi S;Virmouni SA;Pook MA
DNA甲基化主要发生在人类细胞内，作为CpG二核苷酸中胞嘧啶碱基的5-甲基胞嘧啶（5 mC）修饰。5 mC已被证明是一个重要的表观遗传标记，参与控制基因转录的过程，如发育和分化。然而，最近的研究已经确定了一种替代的修饰，5-羟甲基胞嘧啶（5 hmC），这是由10 - 11易位（泰特）酶氧化5 mC形成的。哺乳动物基因组中5 hmC的总体水平约为5 mC水平的10%，尽管在中枢神经系统（CNS）组织中检测到更高的水平。5 hmC的功能还不完全清楚，但有证据表明，5 hmC可能是被动或主动去甲基化过程中去除5 mC的中间产物，也可能是其自身的表观遗传修饰，调节参与神经发育或环境应激反应等过程的染色质或转录因子。本文综述了5 hmC在阿尔茨海默病（AD）、肌萎缩侧索硬化（ALS）、脆性X相关震颤/共济失调综合征（FXTAS）、弗里德赖希共济失调（FRDA）、亨廷顿病（HD）和帕金森病（PD）等神经退行性疾病中的作用。
DNA methylation primarily occurs within human cells as a 5-methylcytosine (5mC) modification of the cytosine bases in CpG dinucleotides. 5mC has proven to be an important epigenetic mark that is involved in the control of gene transcription for processes such as development and differentiation. However, recent studies have identified an alternative modification, 5-hydroxymethylcytosine (5hmC), which is formed by oxidation of 5mC by ten-eleven translocation (TET) enzymes. The overall levels of 5hmC in the mammalian genome are approximately 10% of 5mC levels, although higher levels have been detected in tissues of the central nervous system (CNS). The functions of 5hmC are not yet fully known, but evidence suggests that 5hmC may be both an intermediate product during the removal of 5mC by passive or active demethylation processes and also an epigenetic modification in its own right, regulating chromatin or transcriptional factors involved in processes such as neurodevelopment or environmental stress response. This review highlights our current understanding of the role that 5hmC plays in neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia (FRDA), Huntington's disease (HD), and Parkinson's disease (PD).
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影响因子：
5.9
作者：
DEWAARD, D;BROOKHUIS, KA
通讯作者：
BROOKHUIS, KA
影响因子：
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3.7
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