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A vitamin-C-derived DNA modification catalysed by an algal TET homologue

文献类型：期刊论文

作者Xue, Jian-Huang1; Chen, Guo-Dong1; Hao, Fuhua2; Chen, Hui1,3; Fang, Zhaoyuan1; Chen, Fang-Fang4; Pang, Bo5; Yang, Qing-Lin1; Wei, Xinben6; Fan, Qiang-Qiang1,7
刊名NATURE
出版日期2019-05-23
卷号569期号:7757页码:581-+
ISSN号0028-0836
DOI10.1038/s41586-019-1160-0
通讯作者Huang, Kaiyao(huangky@ihb.ac.cn) ; Tang, Huiru(huiru_tang@fudan.edu.cn) ; Xu, Guo-Liang(glxu@sibcb.ac.cn)
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.
WOS关键词CHLAMYDOMONAS-REINHARDTII ; ASCORBATE BIOSYNTHESIS ; EXPRESSION ANALYSIS ; 5-METHYLCYTOSINE ; GENE ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; 5-FORMYLCYTOSINE ; MECHANISMS ; PROTEINS
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
资助机构National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; Heye Health Technology Inc.
源URL[http://ir.ihb.ac.cn/handle/342005/28106]  
专题水生生物研究所_藻类生物学及应用研究中心
通讯作者Huang, Kaiyao; Tang, Huiru; Xu, Guo-Liang
作者单位1.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
2.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
3.Univ Groningen, Dept Pathol & Med Biol, Univ Med Ctr Groningen, Groningen, Netherlands
4.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai Inst Organ Chem, Shanghai, Peoples R China
5.Chinese Acad Sci, State Key Lab Bioorgan & Nat Prod Chem, Shanghai Inst Organ Chem, Shanghai, Peoples R China
6.Chinese Acad Sci, Key Lab Food Safety Res, INS, Shanghai Inst Biol Sci, Shanghai, Peoples R China
7.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
8.Chinese Acad Sci, Key Lab Computat Biol, Chinese Acad Sci German Max Planck Soc Partner In, Shanghai Inst Biol Sci, Shanghai, Peoples R China
9.Shanghai Normal Univ, Coll Life Sci, Shanghai, Peoples R China
10.Chinese Acad Sci, Key Lab Algal Biol, Inst Hydrobiol, Wuhan, Hubei, 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-+.

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来源：水生生物研究所

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