Epigenetic regulation of sensory axon regeneration after spinal cord injury

Mattéa J. Finelli, Jamie K. Wong, Hongyan Zou

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

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.

Original languageEnglish
Pages (from-to)19664-19676
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number50
DOIs
StatePublished - 2013

Keywords

  • Axon regeneration
  • Conditioning lesion
  • DRG neurons
  • Epigenetic regulation
  • Smad1
  • Spinal cord injury

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