Data from Identification of <i>SULF2</i> as a Novel Transcriptional Target of p53 by Use of Integrated Genomic Analyses

Abstract

<div>Abstract<p>Microarray analysis has been useful for identifying the targets of many transcription factors. However, gene expression changes in response to transcription factor perturbation reveal both direct transcriptional targets and secondary gene regulation. By integrating RNA interference, gene expression profiling, and chromatin immunoprecipitation technologies, we identified a set of 32 direct transcriptional targets of the tumor suppressor p53. Of these 32 genes, 11 are not currently associated with the core p53 pathway. From among these novel pathway members, we focused on understanding the connection between p53 and <i>SULF2</i>, which encodes an extracellular heparan sulfate 6-<i>O</i>-endosulfatase that modulates the binding of growth factors to their cognate receptors and that has been shown to function as a tumor suppressor. Genetic and pharmacologic perturbation of p53 directly influences <i>SULF2</i> expression, and similar to silencing of <i>TP53</i>, RNA interference–mediated suppression of <i>SULF2</i> results in an impaired senescence response of cells to genotoxic stress. Thus, our integrated genomic approach has led to the identification of a novel mediator of p53 network biology. [Cancer Res 2009;69(4):1368–74]</p></div>