The Evolution of Ideas on the Biological Role of 5-methylcytosine Oxidative Derivatives in the Mammalian Genome

In this review, we summarize the data on 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine— cytosine modifications which are produced by TET-mediated oxidation of 5-methylcytosine in DNA. We show the biochemistry of modified cytosine, as well as methods for its global and location analysis. We also highlight the milestones in the evolution of ideas on the biological role of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine in the mammalian genome from their discovery in 2009 to the present time.