Chapter 9 - What Does the Future Hold for the Study of Nucleic Acid Modifications in the Brain?

Abstract

For the past 40years, technological advances have made it possible to interrogate the entire genome; thus, the understanding of DNA modification has evolved significantly. Once considered to be a relatively static epigenetic mechanism, with its primary function restricted to the regulation of transcriptional programming during early cellular development, we now know that DNA methylation is a highly dynamic process in postmitotic neurons and plays a particularly important role in neuronal gene expression that directly impacts behavior. For example, in the adult brain, neuronal activity–induced changes in 5-methylcytosine frequently occur outside gene promoters and 5-hydroxymethylcytosine accounts for almost half of DNA methylation detected in the brain. Moreover, the base sequence can also dictate the relative probability that a region of the genome will be epigenetically modified. This is important because it suggests that gene–epigenetic interactions should be considered in the context of a multilevel and bidirectional landscape, with other epigenetic regulators also acting to coordinate the function of the genome in a cell- and context-specific manner.