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Ascorbic Acid Enhances Tet-Mediated 5-Methylcytosine Oxidation and Promotes DNA Demethylation in Mammals
文献类型：期刊论文
| 作者 | Yin, RC; Mao, SQ; Zhao, BL; Chong, ZC; Yang, Y; Zhao, C; Zhang, DP; Huang, H; Gao, J; Li, Z |
| 刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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| 出版日期 | 2013 |
| 卷号 | 135期号:28页码:10396-10403 |
| 通讯作者 | Wang, HL (reprint author), Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China.,hlwang@rcees.ac.cn |
| 英文摘要 | 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. |
| 学科主题 | Chemistry |
| 类目[WOS] | Chemistry, Multidisciplinary |
| 关键词[WOS] | EMBRYONIC STEM-CELLS ; PATERNAL GENOME ; ACTIVE-DEMETHYLATION ; 5-HYDROXYMETHYLCYTOSINE ; PROTEINS ; DYNAMICS ; 5-CARBOXYLCYTOSINE ; METHYLATION ; MECHANISMS ; GENE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000322103000048 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/471]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Yin, RC,Mao, SQ,Zhao, BL,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, RC.,Mao, SQ.,Zhao, BL.,Chong, ZC.,Yang, Y.,...&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, RC,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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