Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian development and cancer.

5-Hydroxymethylcytosine (5hmC) is an oxidative product of 5-methylcytosine (5mC), catalyzed by the ten eleven translocation (TET) family of enzymes. Although 5hmC was discovered several decades ago, it was only after its recent identification in murine brain and stem cell DNA that it has become a major focus of epigenomic research. Part of the reason for this delay is due to the difficulty in detecting both global and locus-specific 5hmC levels. Several studies have addressed this issue with the development of novel techniques to locate and measure 5hmC, which led to multiple reports detailing 5hmC patterns in stem cells and global 5hmC levels during embryogenesis. Based on these studies of 5hmC levels and reports of tissue-specific TET expression, these enzymes are thought to play a role in mammalian development and differentiation. In addition, the TET enzymes are mutated in several types of cancer, affecting their activity and likely altering genomic 5hmC and 5mC patterns. Furthermore, oxidation of 5mC appears to be a step in several active DNA demethylation pathways, which may be important for normal processes, as well as global hypomethylation during cancer development and progression. Much has been revealed about this interesting DNA modification in recent years, but more research is needed for understanding the role of TET proteins and 5hmC in gene regulation and disease.