The role of epigenetic DNA modifications in the brain: Focus on cell specification, neuropathology, and environmental influences.

Epigenetics plays a fundamental role in the regulation of transcriptional landscapes that define cellular identity and the ability of cells and tissues, and ultimately organisms, to adapt to a changing environment. DNA methylation is a stable and heritable epigenetic mark that is involved in cellular differentiation and homeostasis; nevertheless, methylation marks can be reversed by oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and other derivatives, through the action of TET (ten-eleven translocation) dioxygenase enzymes. This provides a mechanism for the active DNA demethylation observed in key developmental stages, where epigenetic reprogramming events take place, and in postmitotic mature neurons, contributing to brain plasticity. Several lines of evidence, both from animal models and human diseases, enhance our understanding of the essential roles of epigenetic modifiers in brain functions and further strengthen the importance of considering these molecular pathways as therapeutic targets in neuropsychiatric disorders.