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PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system.
- Source :
-
Nature communications [Nat Commun] 2014 Apr 01; Vol. 5, pp. 3527. Date of Electronic Publication: 2014 Apr 01. - Publication Year :
- 2014
-
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.
- Subjects :
- Acetylation
Animals
Female
Histones metabolism
Humans
Male
Mice
Mice, Knockout genetics
Spinal Cord Injuries genetics
Spinal Cord Injuries physiopathology
p300-CBP Transcription Factors genetics
Axons enzymology
Central Nervous System physiology
Epigenesis, Genetic
Nerve Regeneration
Spinal Cord Injuries enzymology
p300-CBP Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 24686445
- Full Text :
- https://doi.org/10.1038/ncomms4527