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

Jian-Huang Xue, Guo-Dong Chen, Fuhua Hao, Hui Chen, Zhaoyuan Fang, Fang-Fang Chen, Bo Pang, Qing-Lin Yang, Xinben Wei, Qiang-Qiang Fan, Changpeng Xin, Jiaohong Zhao, Xuan Deng, Bang-An Wang, Xiao-Jie Zhang, Yueying Chu, Hui Tang, Huiyong Yin, Weimin Ma, Luonan Chen, Jianping Ding, Elmar Weinhold, Rahul M. Kohli, Wen Liu, Zheng-Jiang Zhu, Kaiyao Huang (), Huiru Tang () and Guo-Liang Xu ()
Additional contact information
Jian-Huang Xue: University of Chinese Academy of Sciences
Guo-Dong Chen: University of Chinese Academy of Sciences
Fuhua Hao: Wuhan Institute of Physics and Mathematics
Hui Chen: University of Chinese Academy of Sciences
Zhaoyuan Fang: University of Chinese Academy of Sciences
Fang-Fang Chen: Shanghai Institute of Organic Chemistry
Bo Pang: Shanghai Institute of Organic Chemistry
Qing-Lin Yang: University of Chinese Academy of Sciences
Xinben Wei: Institute for Nutritional Sciences (INS), Shanghai Institutes for Biological Sciences
Qiang-Qiang Fan: University of Chinese Academy of Sciences
Changpeng Xin: Shanghai Institutes of Biological Sciences
Jiaohong Zhao: Shanghai Normal University
Xuan Deng: Institute of Hydrobiology
Bang-An Wang: University of Chinese Academy of Sciences
Xiao-Jie Zhang: University of Chinese Academy of Sciences
Yueying Chu: Wuhan Institute of Physics and Mathematics
Hui Tang: University of Chinese Academy of Sciences
Huiyong Yin: Institute for Nutritional Sciences (INS), Shanghai Institutes for Biological Sciences
Weimin Ma: Shanghai Normal University
Luonan Chen: University of Chinese Academy of Sciences
Jianping Ding: University of Chinese Academy of Sciences
Elmar Weinhold: RWTH Aachen University
Rahul M. Kohli: University of Pennsylvania
Wen Liu: Shanghai Institute of Organic Chemistry
Zheng-Jiang Zhu: Shanghai Institute of Organic Chemistry
Kaiyao Huang: Institute of Hydrobiology
Huiru Tang: Wuhan Institute of Physics and Mathematics
Guo-Liang Xu: University of Chinese Academy of Sciences

Nature, 2019, vol. 569, issue 7757, 581-585

Abstract: Abstract 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 mammals1,2. 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-X-Asp, which is conserved in Fe-dependent dioxygenases3. However, unlike previously described TET enzymes, which use 2-oxoglutarate as a co-substrate4, 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1160-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:569:y:2019:i:7757:d:10.1038_s41586-019-1160-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1160-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().