Abstracts (poster) - Wissenschaft Online

Andrea Tedeschi, Tuan Nguyen, Radhika Puttagunta, Perrine Gaub, Simone Di
Giovanni
Identification of a novel transcription module for axon
outgrowth and regeneration
Transcription plays an important role during neurite and axon outgrowth and
regeneration.
However, to date, no transcriptional complexes have been shown to control axon
outgrowth and regeneration by regulating axon growth genes. Here, we investigate the
role of the tumor suppressor p53 and the histone acetyltransferases CBP/p300 and
P/CAF, which promote chromatin relaxation and promoter accessibility, on axon
outgrowth and regeneration.
We show that specifically p53 and CBP/p300 form a transcriptional complex that
regulates the growth associated protein 43 (GAP-43), a key factor for axon outgrowth
and regeneration, by occupying its promoter. Acetylated p53 at K372-3-82 promotes
neurite outgrowth, and induces GAP-43 expression by binding specific elements on the
neuronal GAP-43 promoter in a chromatin environment via CBP/p300 signaling.
Importantly, in an axon regeneration model, CBP and p53 K372-3-82 are induced in
axotomized 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
wt 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.
contact:
Simone Di Giovanni
Univeristy of Tuebingen
Hertie Institute for Clinical Brain Research
simone.digiovanni@medizin.uni-tuebingen.de
otfried mueller strasse 27
76072 Tuebingen (Germany)