Epigenetics in neuronal regeneration

Damage to neuronal tissues in mammals leads to permanent loss of tissue function that can have major health consequences. While mammals have no inherent regenerative capacity to functionally repair neuronal tissue, other species such as amphibians and teleost fish readily replace damaged tissue. The exploration of development and native regeneration can thus inform the process of inducing regeneration in non-regenerative systems, which can be used to develop new therapeutics. Increasing evidence points to an epigenetic component in the regulation of the changes in cellular gene expression necessary for regeneration. In this review, we compare evidence of epigenetic roles in development and regeneration of neuronal tissue. We have focused on three key systems of important clinical significance: the neural retina, the inner ear, and the spinal cord in regenerative and non-regenerative species. While evidence for epigenetic regulation of regeneration is still limited, changes in DNA accessibility, histone acetylation and DNA methylation have all emerged as key elements in this process. To date, most studies have used broadly acting experimental manipulations to establish a role for epigenetics in regeneration, but the advent of more targeted approaches to modify the epigenome will be critical to dissecting the relative contributions of these regulatory factors in this process and the development of methods to stimulate the regeneration in those organisms like ourselves where only limited regeneration occurs in these neural systems.