An evolving view of epigenetic complexity in the brain

Recent scientific advances have revolutionized our understanding of classical epigenetic mechanisms and the broader landscape of molecular interactions and cellular functions that are inextricably linked to these processes. Our current view of epigenetics includes an increasing appreciation for the dynamic nature of DNA methylation, active mechanisms for DNA demethylation, differential functions of 5-methylcytosine and its oxidized derivatives, the intricate regulatory logic of histone post-translational modifications, the incorporation of histone variants into chromatin, nucleosome occupancy and dynamics, and direct links between cellular signalling pathways and the actions of chromatin 'reader', 'writer' and 'eraser' molecules. We also have an increasing awareness of the seemingly ubiquitous roles played by diverse classes of selectively expressed non-coding RNAs in transcriptional, post-transcriptional, post-translational and local and higher order chromatin modulatory processes. These perspectives are still evolving with novel insights continuing to emerge rapidly (e.g. those related to epigenetic regulation of mobile genetic elements, epigenetic mechanisms in mitochondria, roles in nuclear architecture and 'RNA epigenetics'). The precise functions of these epigenetic factors/phenomena are largely unknown. However, it is unequivocal that they serve as key mediators of brain complexity and flexibility, including neural development and aging, cellular differentiation, homeostasis, stress responses, and synaptic and neural network connectivity and plasticity.