| Ascorbic Acid Enhances Tet-Mediated 5-Methylcytosine Oxidation and Promotes DNA Demethylation in Mammals | |
Yin, Ruichuan; Mao, Shi-Qing; Zhao, Bailin; Chong, Zechen; Yang, Ying; Zhao, Chao; Zhang, Dapeng ; Huang, Hua; Gao, Juan; Li, Zheng; Jiao, Yan; Li, Cuiping; Liu, Shengquan; Wu, Danni; Gu, Weikuan; Yang, Yun-Gui; Xu, Guo-Liang; Wang, Hailin; Wang, HL
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| 2013 | |
| Source Publication | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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| Volume | 135Issue:28Pages:10396-10403 |
| Abstract | DNA hydroxymethylation and its mediated DNA demethylation are critical for multiple cellular processes, for example, nuclear reprogramming, embryonic development, and many diseases. Here, we demonstrate that a vital nutrient ascorbic acid (AA), or vitamin C (Vc), can directly enhance the catalytic activity of Tet dioxygenases for the oxidation of 5-methylcytosine (5mC). As evidenced by changes in intrinsic fluorescence and catalytic activity of Tet2 protein caused by AA and its oxidation-resistant derivatives, we further show that AA can uniquely interact with the C-terminal catalytic domain of Tet enzymes, which probably promotes their folding and/or recycling of the cofactor Fe2+. Other strong reducing chemicals do not have a similar effect. These results suggest that AA also acts as a cofactor of Tet enzymes. In mouse embryonic stem cells, AA significantly increases the levels of all 5mC oxidation products, particularly 5-formylcytosine and 5-carboxylcytosine (by more than an order of magnitude), leading to a global loss of 5mC (similar to 40%). In cells deleted of the Tet1 and Tet2 genes, AA alters neither 5mC oxidation nor the overall level of 5mC. The AA effects are however restored when Tet2 is re-expressed in the Tet-deficient cells. The enhancing effects of AA on 5mC oxidation and DNA demethylation are also observed in a mouse model deficient in AA synthesis. Our data establish a direct link among AA, Tet, and DNA methylation, thus revealing a role of AA in the regulation of DNA modifications. |
| Department | 环境化学与生态毒理学国家重点实验室 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | https://ir.rcees.ac.cn/handle/311016/7486 |
| Collection | 环境化学与生态毒理学国家重点实验室 |
| Corresponding Author | Wang, HL |
| Recommended Citation GB/T 7714 | Yin, Ruichuan,Mao, Shi-Qing,Zhao, Bailin,et al. Ascorbic Acid Enhances Tet-Mediated 5-Methylcytosine Oxidation and Promotes DNA Demethylation in Mammals[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2013,135(28):10396-10403. |
| APA | Yin, Ruichuan.,Mao, Shi-Qing.,Zhao, Bailin.,Chong, Zechen.,Yang, Ying.,...&Wang, HL.(2013).Ascorbic Acid Enhances Tet-Mediated 5-Methylcytosine Oxidation and Promotes DNA Demethylation in Mammals.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,135(28),10396-10403. |
| MLA | Yin, Ruichuan,et al."Ascorbic Acid Enhances Tet-Mediated 5-Methylcytosine Oxidation and Promotes DNA Demethylation in Mammals".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 135.28(2013):10396-10403. |
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