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Nat Commun. 2014 Apr 1;5:3527. doi: 10.1038/ncomms4527.

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

Author information

1
1] Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany [2].
2
1] Department of Axonal Growth and Regeneration, German Center for Neurodegenerative Disease, 53175 Bonn, Germany [2].
3
1] Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany [2] Graduate School for Cellular and Molecular Neuroscience, University of Tu¨bingen, 72076 Tu¨bingen, Germany.
4
1] Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany [2] Division of Brain Sciences, Department of Medicine, Imperial College London, Hammersmith Campus, London W12 ONN, UK.
5
Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
6
1] Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany [2] Graduate School for Cellular and Molecular Neuroscience, University of Tu¨bingen, 72076 Tu¨bingen, Germany [3] DZNE, German Center for Neurodegenerative Diseases, D-72076 Tu¨bingen, Germany.
7
Department of Axonal Growth and Regeneration, German Center for Neurodegenerative Disease, 53175 Bonn, Germany.
8
Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Université de Strasbourg-CNRS, GDR CNRS, Strasbourg 67000, France.

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.

PMID:
24686445
DOI:
10.1038/ncomms4527
[Indexed for MEDLINE]

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