Epigenetic Regulation of Sensory Axon Regeneration after Spinal Cord Injury

Finelli, M. J.; Wong, J. K.; Zou, H.

Abstract

Axon regeneration is hindered by a decline of intrinsic axon growth capability in mature neurons. Reversing this decline is associated with the induction of a large repertoire of regeneration-associated genes (RAGs), but the underlying regulatory mechanisms of the transcriptional changes are largely unknown. Here, we establish a correlation between diminished axon growth potential and histone 4 (H4) hypoacetylation. When neurons are triggered into a growth state, as in the conditioning lesion paradigm, H4 acetylation is restored, and RAG transcription is initiated. We have identified a set of target genes of Smad1, a proregenerative transcription factor, in conditioned DRG neurons. We also show that, during the epigenetic reprogramming process, histone-modifying enzymes work together with Smad1 to facilitate transcriptional regulation of RAGs. Importantly, targeted pharmacological modulation of the activity of histone-modifying enzymes, such as histone deacetylases, leads to induction of multiple RAGs and promotion of sensory axon regeneration in a mouse model of spinal cord injury. Our findings suggest epigenetic modulation as a potential therapeutic strategy to enhance axon regeneration.

Citation

Finelli, M. J., Wong, J. K., & Zou, H. (2013). Epigenetic Regulation of Sensory Axon Regeneration after Spinal Cord Injury. Journal of Neuroscience, 33(50), 19664-19676. https://doi.org/10.1523/jneurosci.0589-13.2013

• Journal Article Type: Article
• Acceptance Date: Nov 6, 2013
• Online Publication Date: Dec 11, 2013
• Publication Date: Dec 11, 2013
• Deposit Date: Jul 25, 2021
• Journal: Journal of Neuroscience
• Electronic ISSN: 1529-2401
• Publisher: Society for Neuroscience
• Peer Reviewed: Peer Reviewed
• Volume: 33
• Issue: 50
• Pages: 19664-19676
• DOI: https://doi.org/10.1523/jneurosci.0589-13.2013
• Keywords: General Neuroscience
• Public URL: https://nottingham-repository.worktribe.com/output/5832683