BMC Genomics Research article NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiation Christopher Brynczka1,2, Paul Labhart3 and B Alex Merrick*1 Address: 1National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA, 2Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27606, USA and 3Genpathway, Inc., San Diego, California 92121, USA Email: Christopher Brynczka - brynczka@niehs.nih.gov; Paul Labhart - plabhart@genpathway.com; B Alex Merrick* - merrick@niehs.nih.gov * Corresponding author Published: 31 May 2007 BMC Genomics 2007, 8:139 doi:10.1186/1471-2164-8-139 This article is available from: http://www.biomedcentral.com/1471-2164/8/139 Received: 13 February 2007 Accepted: 31 May 2007 © 2007 Brynczka et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. BioMed Central Open Access Abstract Background: 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. Results: 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 wnt7b involved in dendritic extension and the tfcp2l4/grhl3 grainyhead homolog implicated in ectodermal development. Additional targets included brk, sdk2, sesn3, txnl2, dusp5, pon3, lect1, pkcbpb15 and other genes. Conclusion: Within the PC12 neuronal context, putative p53-occupied genomic loci spanned the entire Rattus norvegicus 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. Background The tumor suppressor p53 is recognized as a critical regu- lator of cell cycle progression and apoptosis, incorporat- ing signals from DNA damage and other cellular stressors to decide cell fate [1]. Disruption of p53 activity through direct mutation or regulatory dysfunction is a demon- strated causal factor in a large proportion of human malig- nancies [2]. As a transcription factor, many of the functional cellular roles of the p53 protein are elicited through direct DNA binding to sequence-specific cis-regu- latory elements [3] leading to the transactivation or tran- srepression of target genes. Many of these target genes have been described through both computational and biochemical methods [4-7]. Page 1 of 17 (page number not for citation purposes)