| Summary: | <p>Abstract</p> <p>Background</p> <p>p53 is recognized as a critical regulator of the cell cycle and apoptosis. Mounting evidence also suggests a role for p53 in differentiation of cells including neuronal precursors. We studied the transcriptional role of p53 during nerve growth factor-induced differentiation of the PC12 line into neuron-like cells. We hypothesized that p53 contributed to PC12 differentiation through the regulation of gene targets distinct from its known transcriptional targets for apoptosis or DNA repair.</p> <p>Results</p> <p>Using a genome-wide chromatin immunoprecipitation cloning technique, we identified and validated 14 novel p53-regulated genes following NGF treatment. The data show p53 protein was transcriptionally activated and contributed to NGF-mediated neurite outgrowth during differentiation of PC12 cells. Furthermore, we describe stimulus-specific regulation of a subset of these target genes by p53. The most salient differentiation-relevant target genes included <it>wnt7b </it>involved in dendritic extension and the <it>tfcp2l4/grhl3 </it>grainyhead homolog implicated in ectodermal development. Additional targets included <it>brk</it>, <it>sdk2</it>, <it>sesn3</it>, <it>txnl2</it>, <it>dusp5</it>, <it>pon3</it>, <it>lect1</it>, <it>pkcbpb15 </it>and other genes.</p> <p>Conclusion</p> <p>Within the PC12 neuronal context, putative p53-occupied genomic loci spanned the entire <it>Rattus norvegicus </it>genome upon NGF treatment. We conclude that receptor-mediated p53 transcriptional activity is involved in PC12 differentiation and may suggest a contributory role for p53 in neuronal development.</p>
|
|---|