PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system

Radhika Puttagunta (), Andrea Tedeschi, Marilia Grando Sória, Arnau Hervera, Ricco Lindner, Khizr I. Rathore, Perrine Gaub, Yashashree Joshi, Tuan Nguyen, Antonio Schmandke, Claudia J. Laskowski, Anne-Laurence Boutillier, Frank Bradke and Simone Di Giovanni ()
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Radhika Puttagunta: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Andrea Tedeschi: German Center for Neurodegenerative Disease
Marilia Grando Sória: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Arnau Hervera: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Ricco Lindner: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Khizr I. Rathore: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Perrine Gaub: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Yashashree Joshi: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Tuan Nguyen: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Antonio Schmandke: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen
Claudia J. Laskowski: German Center for Neurodegenerative Disease
Anne-Laurence Boutillier: Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg-CNRS, GDR CNRS
Frank Bradke: German Center for Neurodegenerative Disease
Simone Di Giovanni: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract Axonal regenerative failure is a major cause of neurological impairment following central nervous system (CNS) but not peripheral nervous system (PNS) injury. Notably, PNS injury triggers a coordinated regenerative gene expression programme. However, the molecular link between retrograde signalling and the regulation of this gene expression programme that leads to the differential regenerative capacity remains elusive. Here we show through systematic epigenetic studies that the histone acetyltransferase p300/CBP-associated factor (PCAF) promotes acetylation of histone 3 Lys 9 at the promoters of established key regeneration-associated genes following a peripheral but not a central axonal injury. Furthermore, we find that extracellular signal-regulated kinase (ERK)-mediated retrograde signalling is required for PCAF-dependent regenerative gene reprogramming. Finally, PCAF is necessary for conditioning-dependent axonal regeneration and also singularly promotes regeneration after spinal cord injury. Thus, we find a specific epigenetic mechanism that regulates axonal regeneration of CNS axons, suggesting novel targets for clinical application.

Date: 2014
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DOI: 10.1038/ncomms4527

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