TET-family dioxygenases, immune responses and cancer

In 2009, our lab reported that enzymes of the TET (Ten-Eleven Translocation) family were a new class of epigenetic regulators that altered the modification status of cytosine bases in DNA . The three mammalian TET enzymes – TET1 , TET2 and TET3 – successively oxidize the methyl group of 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). These modified cytosine bases (together termed oxidized methylcytosines, oxi-mC) facilitate DNA demethylation and are also novel epigenetic marks. DNA methylation has long been linked to developmental processes and to oncogenesis; similarly TET proteins, which alter DNA modification status, are implicated in numerous biological processes, including cell lineage specification, embryonic development, immune and neuronal function, “stemness” somatic cell reprogramming and cancer. I will discuss the relation between TET activity, DNA modification status and oncogenesis in several model systems with TET loss-of-function.

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