PCAF-dependent epigenetic changes promote axonal regeneration in the central nervous system
| Autor: | Andrea Tedeschi, Radhika Puttagunta, Yashashree Joshi, Marilia Grando Sória, Antonio Schmandke, Tuan Nguyen, Perrine Gaub, Anne-Laurence Boutillier, Arnau Hervera, Khizr I. Rathore, Ricco Lindner, Frank Bradke, Simone Di Giovanni, Claudia J. Laskowski |
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| Přispěvatelé: | Neurology, Grup de Neurofarmacologia Molecular, Universitat Autònoma de Barcelona (UAB), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Central Nervous System
Male metabolism [Histones] genetics [Mice Knockout] genetics [p300-CBP Transcription Factors] Central nervous system General Physics and Astronomy General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Histones Mice physiopathology [Spinal Cord Injuries] medicine Animals Humans p300-CBP Transcription Factors Epigenetics Spinal Cord Injuries ComputingMilieux_MISCELLANEOUS metabolism [p300-CBP Transcription Factors] Mice Knockout Histone Acetyltransferase p300 Multidisciplinary biology genetics [Spinal Cord Injuries] Regeneration (biology) Acetylation General Chemistry Molecular biology Axons physiology [Central Nervous System] Cell biology Nerve Regeneration Histone medicine.anatomical_structure PCAF Peripheral nervous system enzymology [Axons] biology.protein Retrograde signaling p300-CBP-associated factor Female [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ddc:500 enzymology [Spinal Cord Injuries] |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2014, 5 (1), ⟨10.1038/ncomms4527⟩ Nature Communications 5(1), 3527 (2014). doi:10.1038/ncomms4527 |
| ISSN: | 2041-1723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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