A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration.
Transcription regulates axon outgrowth and regeneration. However, to date, no transcription complexes have been shown to control axon outgrowth and regeneration by regulating axon growth genes. Here, we report that the tumor suppressor p53 and its acetyltransferases CBP/p300 form a transcriptional complex that regulates the axonal growth-associated protein 43, a well-characterized pro-axon outgrowth and regeneration protein. Acetylated p53 at K372-3-82 drives axon outgrowth, GAP-43 expression, and binds specific elements on the neuronal GAP-43 promoter in a chromatin environment through CBP/p300 signaling. Importantly, in an axon regeneration model, both CBP and p53 K372-3-82 are induced following axotomy in facial motor neurons, where p53 K372-3-82 occupancy of GAP-43 promoter is enhanced as shown by in vivo chromatin immunoprecipitation. Finally, by comparing wild-type and p53 null mice, we demonstrate that the p53/GAP-43 transcriptional module is specifically switched on during axon regeneration in vivo. These data contribute to the understanding of gene regulation in axon outgrowth and may suggest new molecular targets for axon regeneration.
Tedeschi
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A
Laboratory for NeuroRegeneration and Repair, Department of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried-Mueller Strasse 27, Tuebingen, Germany.
Nguyen
T
T
Puttagunta
R
R
Gaub
P
P
Di Giovanni
S
S
D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D005455:Fluorescent Antibody Technique; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000502:physiology; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019922:GAP-43 Protein; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors