The study identifies TET proteins, particularly TET1, as enzymes that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC) in mammalian DNA. TET1 is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme, and its overexpression in cultured cells results in decreased 5mC levels. hmC is detected in mouse embryonic stem (ES) cells and its levels decrease upon RNA interference-mediated depletion of TET1. The presence and regulation of hmC suggest potential roles for TET proteins in epigenetic regulation through the conversion of 5mC to hmC. The study also highlights the importance of TET proteins in maintaining genomic stability and their potential involvement in diseases such as hematologic malignancies.The study identifies TET proteins, particularly TET1, as enzymes that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC) in mammalian DNA. TET1 is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme, and its overexpression in cultured cells results in decreased 5mC levels. hmC is detected in mouse embryonic stem (ES) cells and its levels decrease upon RNA interference-mediated depletion of TET1. The presence and regulation of hmC suggest potential roles for TET proteins in epigenetic regulation through the conversion of 5mC to hmC. The study also highlights the importance of TET proteins in maintaining genomic stability and their potential involvement in diseases such as hematologic malignancies.