Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders.

The evolving field of neuroepigenetics provides important insights into the molecular foundations of brain function. Novel sequencing technologies have identified patient-specific mutations and gene expression profiles involved in shaping the epigenetic landscape during neurodevelopment and in disease. Traditional methods to investigate the consequences of chromatin-related mutations provide valuable phenotypic insights but often lack information on the biochemical mechanisms underlying these processes. Recent studies, however, are beginning to elucidate how structural and/or functional aspects of histone, DNA, and RNA post-translational modifications affect transcriptional landscapes and neurological phenotypes. Here, we review the identification of epigenetic regulators from genomic studies of brain disease, as well as mechanistic findings that reveal the intricacies of neuronal chromatin regulation. We then discuss how these mechanistic studies serve as a guideline for future neuroepigenetics investigations. We end by proposing a roadmap to future therapies that exploit these findings by coupling them to recent advances in targeted therapeutics.