Excision of 5-hydroxymethylcytosine by DEMETER family DNA glycosylases.

Excision of 5-hydroxymethylcytosine by DEMETER family DNA glycosylases.
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DOI:
10.1016/j.bbrc.2014.03.060
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发表时间:
2014-04-18
影响因子:
3.1
通讯作者:
Huh, Jin Hoe
Huh, Jin Hoe
中科院分区:
生物学4区
文献类型:
--
作者:
Jang, Hosung;Shin, Hosub;Eichman, Brandt F.;Huh, Jin Hoe

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在植物和动物中,5-甲基胞嘧啶 (5mC) 作为表观遗传标记来抑制基因表达,在细胞分化和转座子沉默中发挥关键作用。哺乳动物还含有 5-羟甲基胞嘧啶 (5hmC),是由 TET 家族酶对 5mC 进行羟基化而产生的。 5hmC 在小鼠浦肯野神经元和胚胎干细胞中含量丰富,被认为是哺乳动物活性 DNA 去甲基化的重要中间体。然而,植物中5hmC的存在尚未得到明确证实。在拟南芥中,DEMETER (DME) 家族 DNA 糖基化酶可有效去除 5mC,从而导致 DNA 去甲基化和靶基因转录激活。在这里,我们表明 DME 和 ROS1 在体外具有显着的 5hmC 切除活性,尽管我们在拟南芥中没有检测到 5hmC,这表明植物不太可能利用 5hmC 作为 DNA 去甲基化中间体。我们的结果表明,植物和动物都有 5mC 共同点,但 DNA 去甲基化系统以不同的机制独立进化。
In plants and animals, 5-methylcytosine (5mC) serves as an epigenetic mark to repress gene expression, playing critical roles for cellular differentiation and transposon silencing. Mammals also have 5-hydroxymethylcytosine (5hmC), resulting from hydroxylation of 5mC by TET family-enzymes. 5hmC is abundant in mouse Purkinje neurons and embryonic stem cells, and regarded as an important intermediate for active DNA demethylation in mammals. However, the presence of 5hmC in plants has not been clearly demonstrated. In Arabidopsis, the DEMETER (DME) family DNA glycosylases efficiently remove 5mC, which results in DNA demethylation and transcriptional activation of target genes. Here we show that DME and ROS1 have a significant 5hmC excision activity in vitro, although we detected no 5hmC in Arabidopsis, suggesting that it is very unlikely for plants to utilize 5hmC as a DNA demethylation intermediate. Our results indicate that both plants and animals have 5mC in common but DNA demethylation systems have independently evolved with distinct mechanisms.
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