The Neuroepigenome: Implications of Chemical and Physical Modifications of Genomic DNA in Schizophrenia.

Schizophrenia is a chronic mental illness with a substantial genetic component. To unfold the complex etiology of schizophrenia, it is important to understand the interplay between genetic and nongenetic factors. Genetic factors involve variation in the DNA sequences of protein-coding genes, which directly contribute to phenotypic traits, and variation in noncoding sequences, which comprise 98% of the genome and contain DNA elements known to play a role in regulating gene expression. The epigenome refers to the chemical modifications on both DNA and the structural proteins that package DNA into the nucleus, which together regulate gene expression in specific cell types, conditions, and developmental stages. The dynamic nature of the epigenome makes it an ideal tool to investigate the relationship between inherited genetic mutations associated with schizophrenia and altered gene regulation throughout the course of brain development. In this review, we focus on the current understanding of the role of epigenetic marks and their three-dimensional nuclear organization in the developmental trajectory of distinct brain cell types to decipher the complex gene regulatory mechanisms that are disrupted in schizophrenia.