Epigenetic control of oligodendrocyte development: adding new players to old keepers

• Most epigenetic events regulating OPC differentiation repress transcription.
• Extrinsic cues initiate epigenetic changes in OPCs leading to differentiation.
• Epigenetic regulation in oligodendrocytes is disrupted in disease states.

Emerging and strengthening evidence suggests an important role of myelin in plasticity and axonal survival. However, the mechanisms regulating progression from oligodendrocyte progenitor cells (OPCs) to myelinating oligodendrocytes remain only partially understood. A series of overlapping yet distinct epigenetic events occur as a proliferating OPC exits the cell cycle, initiates differentiation, and becomes a myelin-forming oligodendrocyte that wraps axons. Here we discuss recent advances towards understanding the epigenetic control of oligodendrocyte development that integrates environmental stimuli. We suggest that OPCs are directly responsive to extrinsic signals due to predominantly euchromatic nuclei, while the heterochromatic nuclei render differentiating and myelinating cells less susceptible to signals modulating the epigenome.