5-Hydroxymethylcytosine: a stable or transient DNA modification?

5-Hydroxymethylcytosine: a stable or transient DNA modification?
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DOI:
10.1016/j.ygeno.2014.08.015
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发表时间:
2014-11
期刊:
影响因子:
4.4
通讯作者:
Pfeifer, Gerd P.
Pfeifer, Gerd P.
中科院分区:
生物学3区
文献类型:
--
作者:
Hahn, Maria A.;Szabo, Piroska E.;Pfeifer, Gerd P.

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DNA碱基5-羟甲基胞嘧啶(5hmC)是由5mC氧化酶(Tet蛋白)对5-羟甲基胞嘧啶(5mC)的酶促氧化产生的。由于5hmC不易被DNA甲基转移酶识别,DNA甲基化可能在DNA复制过程中在5hmC位点丢失。此外,5hmC可以被Tet蛋白进一步氧化,转化为5-甲酰基胞嘧啶和5-羧基胞嘧啶,这两种碱基可以通过碱基切除修复从DNA中去除。完成的途径代表了一个与复制无关的DNA去甲基化周期。然而,DNA碱基5hmC也被认为是相当稳定的,并且在相当大的水平上存在,例如在大脑中,这表明它本身代表了一种可能调节染色质结构和转录的表观遗传标记。聚焦于一些已被充分研究的组织和发育阶段,我们讨论了5hmC作为DNA去甲基化的短暂中间体和作为具有指导作用的修饰DNA碱基的对立观点。
The DNA base 5-hydroxymethylcytosine (5hmC) is produced by enzymatic oxidation of 5-methylcytosine (5mC) by 5mC oxidases (the Tet proteins). Since 5hmC is recognized poorly by DNA methyltransferases, DNA methylation may be lost at 5hmC sites during DNA replication. In addition, 5hmC can be oxidized further by Tet proteins and converted to 5-formylcytosine and 5-carboxylcytosine, two bases that can be removed from DNA by base excision repair. The completed pathway represents a replication-independent DNA demethylation cycle. However, the DNA base 5hmC is also known to be rather stable and occurs at substantial levels, for example in the brain, suggesting that it represents an epigenetic mark by itself that may regulate chromatin structure and transcription. Focusing on a few well-studied tissues and developmental stages, we discuss the opposing views of 5hmC as a transient intermediate in DNA demethylation and as a modified DNA base with an instructive role.
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