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5-Hydroxymethylcytosine: A stable or transient DNA modification?

机译:5-羟甲基胞嘧啶:稳定或瞬时的DNA修饰?

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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 methylationmay 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. (C) 2014 Elsevier Inc. All rights reserved.
机译:DNA碱基5-羟甲基胞嘧啶(5hmC)是通过5mC氧化酶(Tet蛋白)对5-甲基胞嘧啶(5mC)进行酶促氧化而产生的。由于5hmC不能被DNA甲基转移酶识别,因此DNA甲基化可能会在DNA复制过程中在5hmC位点丢失。另外,5hmC可以被Tet蛋白进一步氧化并转化为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。完整的途径代表了不依赖复制的DNA脱甲基循环。然而,也已知DNA碱基5hmC相当稳定,并以相当高的水平发生在例如大脑中,这表明它本身代表了表观遗传标记,可以调节染色质的结构和转录。着眼于一些经过充分研究的组织和发育阶段,我们讨论了5hmC作为DNA去甲基化中的瞬时中间体和具有指导作用的修饰DNA碱基的相反观点。 (C)2014 Elsevier Inc.保留所有权利。

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