A vitamin-C-derived DNA modification catalysed by an algal TET homologue
文献类型：期刊论文
| 作者 | Xue, Jian-Huang5; Chen, Guo-Dong5; Hao, Fuhua6; Chen, Hui5,7; Fang, Zhaoyuan5; Chen, Fang-Fang8; Pang, Bo9; Yang, Qing-Lin5; Wei, Xinben10; Fan, Qiang-Qiang5,11 |
| 刊名 | NATURE
 |
| 出版日期 | 2019-05-23 |
| 卷号 | 569期号:7757页码:581-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/s41586-019-1160-0 |
| 英文摘要 | Methylation of cytosine to 5-methylcytosine (5mC) is a prevalent DNA modification found in many organisms. Sequential oxidation of 5mC by ten-eleven translocation (TET) dioxygenases results in a cascade of additional epigenetic marks and promotes demethylation of DNA in mammals(1,2). However, the enzymatic activity and function of TET homologues in other eukaryotes remains largely unexplored. Here we show that the green alga Chlamydomonas reinhardtii contains a 5mC-modifying enzyme (CMD1) that is a TET homologue and catalyses the conjugation of a glyceryl moiety to the methyl group of 5mC through a carbon-carbon bond, resulting in two stereoisomeric nucleobase products. The catalytic activity of CMD1 requires Fe(ii) and the integrity of its binding motif His-XAsp, which is conserved in Fe-dependent dioxygenases(3). However, unlike previously described TET enzymes, which use 2-oxoglutarate as a co-substrate(4), CMD1 uses l-ascorbic acid (vitamin C) as an essential co-substrate. Vitamin C donates the glyceryl moiety to 5mC with concurrent formation of glyoxylic acid and CO2. The vitamin-C-derived DNA modification is present in the genome of wild-type C. reinhardtii but at a substantially lower level in a CMD1 mutant strain. The fitness of CMD1 mutant cells during exposure to high light levels is reduced. LHCSR3, a gene that is critical for the protection of C. reinhardtii from photo-oxidative damage under high light conditions, is hypermethylated and downregulated in CMD1 mutant cells compared to wild-type cells, causing a reduced capacity for photoprotective non-photochemical quenching. Our study thus identifies a eukaryotic DNA base modification that is catalysed by a divergent TET homologue and unexpectedly derived from vitamin C, and describes its role as a potential epigenetic mark that may counteract DNA methylation in the regulation of photosynthesis. |
| 资助项目 | National Key R&D Program of China[2017YFA0102700] ; National Key R&D Program of China[2017YFC0906800] ; National Science Foundation of China[31830018] ; National Science Foundation of China[31430049] ; National Science Foundation of China[81590953] ; National Science Foundation of China[21575151] ; National Science Foundation of China[91851201] ; Shanghai Municipal Science and Technology Project[2017SHZDZX01] ; Shanghai Municipal Science and Technology Project[16JC1400500] ; Chinese Academy of Sciences[XDB19010102] ; NIH[R01-GM118501] ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000468844100056 |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7758]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Huang, Kaiyao; Tang, Huiru; Xu, Guo-Liang |
| 作者单位 | 1.Fudan Univ, Sch Life Sci, Human Phenome Inst, Shanghai Int Ctr Mol Phen,Collaborat Innovat Ctr, Shanghai, Peoples R China 2.Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA 3.Fudan Univ, State Key Lab Genet Engn, Zhongshan Hosp, Shanghai, Peoples R China 4.Fudan Univ, Key Lab Med Epigenet & Metab, Inst Biomed Sci, Shanghai Med Coll, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, State Key Lab Mol Biol, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,Chinese Acad Sc, Shanghai, Peoples R China 6.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Inst Phys & Math, Wuhan, Hubei, Peoples R China 7.Univ Groningen, Dept Pathol & Med Biol, Univ Med Ctr Groningen, Groningen, Netherlands 8.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai Inst Organ Chem, Shanghai, Peoples R China 9.Chinese Acad Sci, State Key Lab Bioorgan & Nat Prod Chem, Shanghai Inst Organ Chem, Shanghai, Peoples R China 10.Chinese Acad Sci, Key Lab Food Safety Res, INS, Shanghai Inst Biol Sci, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xue, Jian-Huang,Chen, Guo-Dong,Hao, Fuhua,et al. A vitamin-C-derived DNA modification catalysed by an algal TET homologue[J]. NATURE,2019,569(7757):581-+. |
| APA | Xue, Jian-Huang.,Chen, Guo-Dong.,Hao, Fuhua.,Chen, Hui.,Fang, Zhaoyuan.,...&Xu, Guo-Liang.(2019).A vitamin-C-derived DNA modification catalysed by an algal TET homologue.NATURE,569(7757),581-+. |
| MLA | Xue, Jian-Huang,et al."A vitamin-C-derived DNA modification catalysed by an algal TET homologue".NATURE 569.7757(2019):581-+. |
入库方式： OAI收割
来源：武汉植物园
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