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Published on: May 31, 2017
PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system
Radhika Puttagunta1, Andrea Tedeschi2, Marilia Grando Sória3
11] Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany [2].
Peripheral nerve injury triggers gene expression for regeneration, unlike central nervous system injury. This study identifies PCAF as a key epigenetic regulator, linking retrograde signaling to successful axonal regeneration and suggesting new therapeutic targets for CNS repair.
Area of Science:
- Neuroscience
- Epigenetics
- Molecular Biology
Background:
- Axonal regenerative failure after central nervous system (CNS) injury causes significant neurological deficits.
- Peripheral nervous system (PNS) injuries, in contrast, typically allow for axonal regeneration due to a coordinated gene expression program.
Purpose of the Study:
- To elucidate the molecular mechanisms linking retrograde signaling to the differential gene expression programs that govern CNS versus PNS axonal regeneration.
- To identify specific epigenetic regulators involved in promoting axonal regeneration.
Main Methods:
- Systematic epigenetic studies, including analysis of histone acetylation.
- Investigation of extracellular signal-regulated kinase (ERK)-mediated retrograde signaling pathways.
- Assessment of the role of p300/CBP-associated factor (PCAF) in axonal regeneration after CNS and PNS injuries.
Main Results:
- PCAF promotes histone 3 Lys 9 acetylation at regeneration-associated gene promoters following peripheral nerve injury, but not central nerve injury.
- ERK-mediated retrograde signaling is essential for PCAF-dependent gene reprogramming related to regeneration.
- PCAF is critical for conditioning-dependent axonal regeneration and can independently promote regeneration after spinal cord injury.
Conclusions:
- A specific epigenetic mechanism involving PCAF and histone acetylation regulates axonal regeneration in the CNS.
- This finding highlights PCAF as a potential therapeutic target for enhancing CNS axonal repair and recovery.
