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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Xu, Guo-Liang1,18; Tang, Huiru2,3,17; Huang, Kaiyao9; Zhu, Zheng-Jiang15; Liu, Wen14; Kohli, Rahul M.4,5; Weinhold, Elmar6; Ding, Jianping7,18; Chen, Luonan8,12,18; Ma, Weimin10
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
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 Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc. ; National Key R&D Program of China ; National Key R&D Program of China ; National Science Foundation of China ; National Science Foundation of China ; Shanghai Municipal Science and Technology Project ; Shanghai Municipal Science and Technology Project ; Chinese Academy of Sciences ; Chinese Academy of Sciences ; NIH ; NIH ; Thousand Youth Talents Program ; Thousand Youth Talents Program ; Agilent Technologies Thought Leader Award ; Agilent Technologies Thought Leader Award ; Heye Health Technology Inc. ; Heye Health Technology Inc.
源URL[http://ir.wipm.ac.cn/handle/112942/13656]  
专题中国科学院武汉物理与数学研究所
通讯作者Xu, Guo-Liang; Tang, Huiru; Huang, Kaiyao
作者单位1.Fudan Univ, Key Lab Med Epigenet & Metab, Inst Biomed Sci, Shanghai Med Coll, Shanghai, Peoples R China
2.Fudan Univ, Sch Life Sci, Human Phenome Inst, Shanghai Int Ctr Mol Phen,Collaborat Innovat Ctr, Shanghai, Peoples R China
3.Fudan Univ, State Key Lab Genet Engn, Zhongshan Hosp, Shanghai, Peoples R China
4.Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA
5.Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
6.Rhein Westfal TH Aachen, Inst Organ Chem, Aachen, Germany
7.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, Inst Biochem & Cell Biol, Shanghai, Peoples R China
8.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China
9.Chinese Acad Sci, Key Lab Algal Biol, Inst Hydrobiol, Wuhan, Hubei, Peoples R China
10.Shanghai Normal Univ, Coll Life Sci, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Guo-Liang,Tang, Huiru,Huang, Kaiyao,et al. A vitamin-C-derived DNA modification catalysed by an algal TET homologue[J]. NATURE,2019,569(7757):581-+.
APA Xu, Guo-Liang.,Tang, Huiru.,Huang, Kaiyao.,Zhu, Zheng-Jiang.,Liu, Wen.,...&Xue, Jian-Huang.(2019).A vitamin-C-derived DNA modification catalysed by an algal TET homologue.NATURE,569(7757),581-+.
MLA Xu, Guo-Liang,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：武汉物理与数学研究所

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