TY  - JOUR
AU  - Puttagunta, Radhika
AU  - Tedeschi, Andrea
AU  - Sória, Marilia Grando
AU  - Hervera, Arnau
AU  - Lindner, Ricco
AU  - Rathore, Khizr I
AU  - Gaub, Perrine
AU  - Joshi, Yashashree
AU  - Nguyen, Tuan
AU  - Schmandke, Antonio
AU  - Laskowski, Claudia J
AU  - Boutillier, Anne-Laurence
AU  - Bradke, Frank
AU  - Di Giovanni, Simone
TI  - PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system.
JO  - Nature Communications
VL  - 5
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-02324
SP  - 3527
PY  - 2014
AB  - 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.
KW  - Acetylation
KW  - Animals
KW  - Axons: enzymology
KW  - Central Nervous System: physiology
KW  - Epigenesis, Genetic
KW  - Female
KW  - Histones: metabolism
KW  - Humans
KW  - Male
KW  - Mice
KW  - Mice, Knockout: genetics
KW  - Nerve Regeneration
KW  - Spinal Cord Injuries: enzymology
KW  - Spinal Cord Injuries: genetics
KW  - Spinal Cord Injuries: physiopathology
KW  - p300-CBP Transcription Factors: genetics
KW  - p300-CBP Transcription Factors: metabolism
KW  - Histones (NLM Chemicals)
KW  - p300-CBP Transcription Factors (NLM Chemicals)
KW  - p300-CBP-associated factor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24686445
DO  - DOI:10.1038/ncomms4527
UR  - https://pub.dzne.de/record/136002
ER  -