DNA Methylation and Adult Neurogenesis

Abstract

The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain. The contributions of DNA methylation and associated proteins to embryonic and adult neurogenesis will be examined. Particular attention will be given to the impact on adult hippocampal neurogenesis (AHN), which is a key mechanism contributing to brain plasticity, learning, memory and mood regulation. DNA methylation influences multiple aspects of neurogenesis from stem cell maintenance and proliferation, fate specification, neuronal differentiation and maturation, and synaptogenesis. In addition, DNA methylation during neurogenesis has been shown to be responsive to many extrinsic signals, both under normal conditions and during disease and injury. Finally, crosstalk between DNA methylation, Methyl-DNA binding domain (MBD) proteins such as MeCP2 and MBD1 and histone modifying complexes is used as an example to illustrate the extensive interconnection between these epigenetic regulatory systems.