TEThered vitamin C

Nature 569, 581–585 (2019)

5-Methylcytosine (5mC) is one of the most prevalent DNA modifications and is associated with negative regulation of gene expression. In mammalian cells, 5mC is removed by a series of oxidation reactions mediated by ten–eleven translocation (TET) dioxygenases, which use 2-oxoglutarate (2-OG) as a co-substrate. Xue et al. identified a TET homolog, CMD1, in the green alga Chlamydomonas reinhardtii that utilizes vitamin C (ascorbate) as an essential co-substrate instead of 2-OG to convert 5mC to a new DNA modification, 5-glycerylmethylcytosine (5gmC). Depletion of CMD1 or the key vitamin C synthesis gene VTC2 reduced the genomic content of 5gmC and increased that of 5mC. Using a luciferase reporter system, the authors revealed that conversion of 5mC to 5gmC reduced downstream gene repression. Functional studies found that loss of CMD1 increased algal sensitivity to light-induced damage by repressing the expression of LHCSR3, a key gene for photoprotection, via increasing methylation in its 5′ region. This study identifies a new functional DNA epigenetic marker and expands our understanding of the reaction mechanisms of oxygenases.

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Correspondence to Yiyun Song.

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Song, Y. TEThered vitamin C. Nat Chem Biol 15, 651 (2019). https://doi.org/10.1038/s41589-019-0319-1

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