DNA Methylation and Hydroxymethylation and Behavior

Environmentally sensitive molecular mechanisms in the brain, such as DNA methylation, have become a significant focus of neuroscience research because of mounting evidence indicating that they are critical in response to social situations, stress, threats, and behavior. The recent identification of 5-hydroxymethylcytosine (5hmC), which is enriched in the brain (tenfold over peripheral tissues), raises new questions as to the role of this base in mediating epigenetic effects in the brain. The development of genome-wide methods capable of distinguishing 5-methylcytosine (5mC) from 5hmC has revealed that a growing number of behaviors are linked to independent disruptions of 5mC and 5hmC levels, further emphasizing the unique importance of both of these modifications in the brain. Here, we review the recent links that indicate DNA methylation (both 5mC and 5hmC) is highly dynamic and that perturbations in this modification may contribute to behaviors related to psychiatric disorders and hold clinical relevance.