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首页> 外文期刊>FEBS Open Bio >Inhibition of DNA methyltransferase leads to increased genomic 5‐hydroxymethylcytosine levels in hematopoietic cells
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Inhibition of DNA methyltransferase leads to increased genomic 5‐hydroxymethylcytosine levels in hematopoietic cells

机译：抑制DNA甲基转移酶导致造血细胞中的基因组5-羟甲基胞嘧啶水平升高

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5‐Hydroxymethylcytosine (5hmC) is produced from 5‐methylcytosine (5mC) by Ten‐eleven translocation (TET) dioxygenases. The epigenetic modification 5hmC has crucial roles in both cellular development and differentiation. The 5hmC level is particularly high in the brain. While 5mC is generally associated with gene silencing/reduced expression, 5hmC is a more permissive epigenetic mark. To understand its physiological function, an easy and accurate quantification method is required. Here, we have developed a novel LC‐MS/MS‐based approach to quantify both genomic 5mC and 5hmC contents. The method is based on the liberation of nucleobases by formic acid. Applying this method, we characterized the levels of DNA methylation and hydroxymethylation in mouse brain and liver, primary hepatocytes, and various cell lines. Using this approach, we confirm that the treatment of different cell lines with the DNA methyltransferase inhibitor 5‐aza‐2′‐deoxycytidine leads to a decrease in 5mC content. This decrease was accompanied by an increase in 5hmC levels in cell lines of hematopoietic origin. Finally, we showed that ascorbate elevates the levels of 5hmC and augments the effect of 5‐aza‐2′‐deoxycytidine without significantly influencing 5mC levels.
机译：5-羟甲基胞嘧啶（5hmC）由十一-甲基易位（TET）双加氧酶从5-甲基胞嘧啶（5mC）产生。表观遗传修饰5hmC在细胞发育和分化中都起着至关重要的作用。 5hmC水平在大脑中特别高。虽然5mC通常与基因沉默/表达降低相关，但5hmC是更宽松的表观遗传标记。为了了解其生理功能，需要一种简单而准确的定量方法。在这里，我们开发了一种新颖的基于LC-MS / MS的方法来定量5mC和5hmC基因组含量。该方法基于甲酸释放核碱基。应用此方法，我们表征了小鼠大脑和肝脏，原代肝细胞和各种细胞系中DNA甲基化和羟甲基化的水平。使用这种方法，我们确认使用DNA甲基转移酶抑制剂5-aza-2'-脱氧胞苷处理不同的细胞系会导致5mC含量降低。这种减少伴随着造血起源细胞系中5hmC水平的增加。最后，我们表明抗坏血酸可提高5hmC的水平并增强5-氮杂-2'-脱氧胞苷的作用，而不会显着影响5mC的水平。

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