Figure 11.

Combined changes of DNA methylation, gene expression, and chromatin states relate to brain development and aging. DNA demethylation of restrictive chromatin and methylation of permissive chromatin activate/deactivate different cell functions with age in a mostly irreversible fashion. Differentiation of neuronal tissue proceeds in active states which then become stabilized after repression of developmental genes. Poised states maintain plasticity while PRC2-repressed states maintain cellular identity of differentiated neuronal tissue. In particular, transitions between the latter states are partly reversible due to (de-)methylation equilibria governed by the activity of methyl writing, erasing and reading enzymes, and a large battery of cofactors such as PRC2.