Epigenetic regulation of brain development, plasticity, and response to early-life stress

Brain development is choreographed by complex gene programs, regulated in turn by epigenetic mechanisms. Far from being complete at birth, both the brain and epigenome continue to mature postnatally. Recent research has found postnatal maturation of the epigenome—including cell-type specific patterns of DNA methylation, chromatin modifications, and non-coding RNAs—to be largely complete by the peri-adolescent period. However, a feature of neurons is their plasticity and dynamic responsiveness to environmental and other signals, and epigenetic mechanisms help govern both critical period and life-long plasticity. Environmental perturbations during development, such as early-life stress, can also become encoded in the epigenome. Evidence from human and non-human animal studies of early-life stress has converged on long-lasting epigenetic changes at several key genes which confer functional changes in stress response, as well as epigenome-wide changes including accelerated epigenetic aging. This review describes epigenetic processes and synthesizes recent literature on postnatal epigenome maturation, the relationship between the epigenome and postnatal sensitive periods and plasticity, and the impact of early-life stress on epigenetic development.