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Researchers Discover Novel Modification of 5mC in Green Algae

DNA methylation is widespread in eukaryotic organisms. Methylation of cytosine to 5-methylcytosine (5mC) and reverse demethylation is related to various biological processes. In mammals, demethylation of 5mC relies on oxidation by TET dioxygenases to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In most organisms, however, neither modes of 5mC processing nor function of TET remains unknown. 

Recently, three research groups led by Prof. XU Guoliang from Shanghai Institute of Biochemistry and Cell Biology, Prof. TANG Huiru from Fudan University, Prof. HUANG Kaiyao from Institute of Hydrobiology (IHB) of Chinese Academy of Sciences collaborated to uncover that in unicellular green algae Chlamydomonas reinhardtii how the TET family protein promote modification of the methyl group in 5mC. The research entitled “A vitamin-C-derived DNA modification catalysed by an algal TET homologue” was published recently in Nature. 

Firstly, researchers identified CMD1 as a TET homologue in Chlamydomonas reinhardtii. The enzyme catalyses the conjugation of a glyceryl moiety to the methyl group of 5mC, with vitamin C as the donator of the glyceryl moiety. For further study, researchers applied CRISPR-Cas9 technology to conclude that the glyceryl 5mC modification could regulate expression of photoprotection gene LHCSR3 through demethylation, thus influence acclimation to high light. 

The discovery of the new mechanism in Chlamydomonas reinhardtii is of great value to the study of eukaryotic DNA methylation. Furthermore, the modification may be used for DNA technologies such as the genome-wide mapping of 5mC because of its selectivity. As to Chlamydomonas reinhardtii, the successful application of CRSIPR-Cas9 in this research will be helpful to other genetic studies.