It was not until 2009 that the existence of 5hmC in mammalian cells was unambiguously proven [
7,
8]. By homology searches against a bacteriophage protein that oxidizes thymine in DNA, Tahiliani
et al. [
8] discovered three proteins, Ten-eleven translocation 1–3 (TET1-3), in mammalian genomes as candidate 5mC oxidases and confirmed such activity for TET1, a gene/protein earlier implicated in a translocation in a myeloid leukemia patient [
9]. These discoveries were breakthroughs in the field of mammalian epigenetics.