THE UNIQUE EPIGENOMIC LANDSCAPE OF THE
CENTRAL NERVOUS SYSTEM
Despite the potentially unique conceptual role of DNA methylation in activity- and experience-
dependent transcriptional reorganization within nondividing neurons, it was once a basic assumption that the overall epigenetic complement of the brain (i.e., the types of modifications and
their meaning with relation to gene expression) was not unique compared to other somatic organs.
Indeed, the brain uses DNA methylation to silence genes in particular cells just as other organs do,
and for the vast majority of the time that epigenetics has constituted its own subdiscipline, it was
unclear precisely how DNA methylation could be reversed absent ongoing cell division (58–61).
However, the past five years have seen remarkable advances in our understanding of the dynamic
nature of DNA methylation processes. Overall, this has generated compelling reasons to believe
that DNA methylation in neurons is mechanistically distinct from DNA methylation in almost all
other cell types in the body.