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DNA methylation and hydroxymethylation at the 5-position of cytosine (5mC) are essential epigenetic alterations that play vital roles in gene expression regulation and cell differentiation. DNA methylation typically represses gene transcription. Hydroxymethylation, on the contrary, activates gene expression or prompts DNA demethylation. 5mC groups introduced by DNA Methyl-Transferases can be iteratively oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the action of Tet Methylcytosine Dioxygenases. 5hmC is the most abundant component in vivo among the three 5mC oxidative derivatives and can be identified in almost all mammalian tissues and cells. 5mC and 5hmC genome-wide mapping uncover the genomic areas of these alterations, which is crucial for elucidating their mechanisms.
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