Chromatin modification and epigenetic control in functional nerve regeneration

The repair and functional recovery of the nervous system is a highly regulated process that requires the coordination of many different components including the proper myelination of regenerated axons. Dysmyelination and remyelination failures after injury result in defective nerve conduction, impairing normal nervous system functions. There are many convergent regulatory networks and signaling mechanisms between development and regeneration. For instance, the regulatory mechanisms required for oligodendrocyte lineage progression could potentially play fundamental roles in myelin repair. In recent years, epigenetic chromatin modifications have been implicated in CNS myelination and functional nerve restoration. The pro-regenerative transcriptional program is likely silenced or repressed in adult neural cells including neurons and myelinating cells in the central and peripheral nervous systems limiting the capacity for repair after injury. In this review, we will discuss the roles of epigenetic mechanisms, including histone modifications, chromatin remodeling, and DNA methylation, in the maintenance and establishment of the myelination program during normal oligodendrocyte development and regeneration. We also discuss how these epigenetic processes impact myelination and axonal regeneration, and facilitate the improvement of current preclinical therapeutics for functional nerve regeneration in neurodegenerative disorders or after injury.