DNA Methylation

One of the fastest growing fields in biology and cancer research is epigenetics. While the underlying genetic code defines which proteins and gene products are synthesized, it is epigenetic control that defines when and where they are expressed. This dynamic control of gene expression is necessary for X chromosome inactivation, embryogenesis, cellular differentiation and appears integral to memory formation and synaptic plasticity. 5-Hydroxymethyl-2'-deoxyCytidine (hmdC), a dC modification, has been detected in Purkinje neurons and embryonic stem cells and was also found to be strongly enriched in brain tissues associated with higher cognitive functions. This dC modification is generated by the action of ?-ketoglutarate dependent ten eleven translocation (TET) enzymes, which oxidize 5-Me-dC to hmdC. This finding stimulated discussion about active demethylation pathways that could occur, e.g., via base excision repair (BER), with the help of specialized DNA glycosylases. Alternatively, one could envision a process in which the hydroxymethyl group of hmdC is further oxidized to 5-formyl-dC (fdC) or 5-carboxy-dC (cadC) followed by elimination of either formic acid or carbon dioxide. And so began the study of DNA epigenetics.