Authors: S. DI GIOVANNI, E. MACLACHLAN, I. PALMISANO, T. HUTSON, A. HERVERA, F. DE VIRGILIIS, M. DANZI, J. BIXBY, V. LEMMON
Regeneration after peripheral nerve injury depends on the activation of key signalling events, the recruitment of transcription factors and histone acetylation. This does not occur after a central spinal injury, which is associated with regenerative failure. Whether specific histone marks and the recruitment of transcription factors confers a differential molecular signature between a central versus a peripheral axonal injury remained to be determined. Here, we performed RNAseq and ChIPseq for H3K27ac and H3K9ac in the sciatic dorsal root ganglia after central spinal cord or peripheral sciatic nerve injury, to identify key molecular events associated with regeneration vs regenerative failure. Data analysis showed that increased promoter enrichment of H3K27ac/H3K9ac occurs across various regenerative associated genes after sciatic injury only. Bioinformatics analysis identified a gene network enriched in transcription factors and histone acetylation.
Indeed, we found that this complex is required for the regenerative growth of sensory neurons including after a spinal injury. Lastly, we identified the FDA approved HDAC inhibitor Panobinostat that activates this network to promote axonal regeneration after spinal cord injury.
*S. DI GIOVANNI1, E. MACLACHLAN1, I. PALMISANO1, T. HUTSON1, A. HERVERA1, F. DE VIRGILIIS1,2, M. DANZI2, J. BIXBY2, V. LEMMON2;
1Imperial Col. London, London,, United Kingdom; 2University of Miami, Miami, FL. Epigenetic regulation of axonal regeneration. Program No. 213.15. 2018 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2018. Online.
Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration Open Access in Neurotherapeutics Palmisano, I. & Di Giovanni, S. Neurotherapeutics (2018) 15: 529. https://doi.org/10.1007/s13311-018-0636-1