CHAPTER 11: The TET/JBP Family of Nucleic Acid Base-Modifying 2-Oxoglutarate and Iron-Dependent Dioxygenases

The TET/JBP family of enzymes includes 2-oxoglutarate- and Fe(ii)-dependent dioxygenases that oxidize 5-methylpyrimidines in nucleic acids. They include euglenozoan JBP enzymes that catalyse the first step in the biosynthesis of the hypermodified thymine, base J, and metazoan TET enzymes that generate oxidized 5-methylcytosines (hydroxy-, formyl- and carboxymethylcytosine) in DNA. Recent studies suggest that these modified bases function as epigenetic marks and/or as potential intermediates for DNA demethylation during resetting of epigenetic 5mC marks upon zygote formation and in primordial germ cell development. Studies in mammalian models also point to an important role for these enzymes in haematopoiesis, tumour suppression, cell differentiation and neural behavioural adaptation. The TET/JBP family has undergone extensive gene expansion in fungi, such as mushrooms, in conjunction with a novel class of transposons and might play a role in genomic plasticity and speciation. Certain versions from stramenopiles and chlorophytes are likely to modify RNA and often show fusions to other RNA-modifying enzymatic domains. The ultimate origin of the TET/JBP family lies in bacteriophages where the enzymes are likely to catalyse formation of modified bases with key roles in DNA packaging and evasion of host restriction.