title: Epigenetic regulation of sensory axon regeneration after spinal cord injury.
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.
authors: Fishberg Department of Neuroscience and Department of Neurosurgery, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors: Mattéa J
authors: MJ
authors: Finelli
authors: Jamie K
authors: JK
authors: Wong
authors: Hongyan
authors: H
authors: Zou
mesh_terms: D000107:Acetylation; D000818:Animals; D001369:Axons / Q000502:physiology*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005727:Ganglia, Spinal / Q000502:physiology; D006657:Histones / Q000235:genetics; D051379:Mice; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000503:physiopathology
chemical_list: D006657:Histones
keywords: DRG neurons; Smad1; axon regeneration; conditioning lesion; epigenetic regulation; spinal cord injury