Ludwigs-Maximilian-Universität München, Butenandtstr. 5-13, 81377, Munich, Germany.
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, CB2 0RE, UK.
Chemistry. 2021 Jun 1;27(31):8100-8104. doi: 10.1002/chem.202100551. Epub 2021 May 1.
The four non-canonical nucleotides in the human genome 5-methyl-, 5-hydroxymethyl-, 5-formyl- and 5-carboxydeoxycytidine (mdC, hmdC, fdC and cadC) form a second layer of epigenetic information that contributes to the regulation of gene expression. Formation of the oxidized nucleotides hmdC, fdC and cadC requires oxidation of mdC by ten-eleven translocation (Tet) enzymes that require oxygen, Fe(II) and α-ketoglutarate as cosubstrates. Although these oxidized forms of mdC are widespread in mammalian genomes, experimental evidence for their presence in fungi and plants is ambiguous. This vagueness is caused by the fact that these oxidized mdC derivatives are also formed as oxidative lesions, resulting in unclear basal levels that are likely to have no epigenetic function. Here, we report the xdC levels in the fungus Amanita muscaria in comparison to murine embryonic stem cells (mESCs), HEK cells and induced pluripotent stem cells (iPSCs), to obtain information about the basal levels of hmdC, fdC and cadC as DNA lesions in the genome.
人类基因组中的四个非 canonical 核苷酸（5-甲基化、5-羟甲基化、5-甲酰基化和 5-羧基去氧胞苷）形成了第二层表观遗传信息，有助于基因表达的调控。这些氧化核苷酸 hmdC、fdC 和 cadC 的形成需要氧、Fe(II)和α-酮戊二酸作为共底物的 ten-eleven translocation (Tet) 酶对 mdC 的氧化。尽管这些氧化形式的 mdC 在哺乳动物基因组中广泛存在，但在真菌和植物中存在这些形式的实验证据是模棱两可的。这种模糊性是由于这些氧化的 mdC 衍生物也作为氧化损伤形成，导致不清楚的基础水平，可能没有表观遗传功能。在这里，我们报告了真菌鹅膏蕈中的 xdC 水平与小鼠胚胎干细胞 (mESCs)、HEK 细胞和诱导多能干细胞 (iPSCs) 的比较，以获得关于基因组中 hmdC、fdC 和 cadC 作为 DNA 损伤的基础水平的信息。
