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

doi:10.1038/s41586-019-1160-0

	A vitamin-C-derived DNA modification catalysed by an algal TET homologue
	Xue, Jian-Huang 1; Chen, Guo-Dong 1; Hao, Fuhua 2; Chen, Hui 1,3; Fang, Zhaoyuan 1; Chen, Fang-Fang 4; Pang, Bo 5; Yang, Qing-Lin 1; Wei, Xinben 6; Fan, Qiang-Qiang1,7 ; Xin, Changpeng 8; Zhao, Jiaohong 9; Deng, Xuan 10; Wang, Bang-An 1; Zhang, Xiao-Jie 1; Chu, Yueying 2; Tang, Hui 1; Yin, Huiyong6,7 ; Ma, Weimin 9; Chen, Luonan1,7,11 ; Ding, Jianping 1,12; Weinhold, Elmar 13; Kohli, Rahul M.14,15; Liu, Wen 5; Zhu, Zheng-Jiang 4; Huang, Kaiyao 10; Tang, Huiru 2,16,17; Xu, Guo-Liang 1,18
	2019-05-23
发表期刊	NATURE (IF:50.5[JCR-2023],54.4[5-Year])
ISSN	0028-0836
卷号	569 期号:7757 页码:581-+
发表状态	已发表
DOI	10.1038/s41586-019-1160-0
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.
收录类别	SCI ; SCIE
语种	英语
资助项目	NIH[R01-GM118501]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000468844100056
出版者	NATURE PUBLISHING GROUP
WOS关键词	CHLAMYDOMONAS-REINHARDTII ; ASCORBATE BIOSYNTHESIS ; EXPRESSION ANALYSIS ; 5-METHYLCYTOSINE ; GENE ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; 5-FORMYLCYTOSINE ; MECHANISMS ; PROTEINS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/45639
专题	生命科学与技术学院_硕士生生命科学与技术学院_特聘教授组_陈洛南组生命科学与技术学院_特聘教授组_尹慧勇组
通讯作者	Tang, Hui; 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 11.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China 12.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, Inst Biochem & Cell Biol, Shanghai, Peoples R China 13.Rhein Westfal TH Aachen, Inst Organ Chem, Aachen, Germany 14.Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA 15.Univ Penn, Dept Biochem & Biophys, Perelman Sch Med, Philadelphia, PA 19104 USA 16.Fudan Univ, State Key Lab Genet Engn, Zhongshan Hosp, Shanghai, Peoples R China 17.Fudan Univ, Sch Life Sci, Human Phenome Inst, Shanghai Int Ctr Mol Phen,Collaborat Innovat Ctr, Shanghai, Peoples R China 18.Fudan Univ, Key Lab Med Epigenet & Metab, Inst Biomed Sci, Shanghai Med Coll, 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-+.