Genome-wide analysis of p63 and mutant p53 in human keratinocytes.

p63 is crucial for the development and maintenance of pluristratified epithelia and p53 is a master regulator of the DNA-damage response, very often mutated in epithelial tumors. haCaT keratinocytes harbor two mutant Gain-of-function -GOF- alleles of p63, H179Y and R282Q. recent data indicate that GOF mutp53 is bound to DNA, through association with p63 and other TFs. to clarify this point, we performed ChIP-Seq for mutp53 and p63 and functional inactivation of mutp53 followed by gene expression analysis. Mutp53 associates with 7133 locations in vivo, 1591 of which are in promoters. Interestingly, the overlap between the two TFs is relatively modest (20%). The functional categories of the genes targeted and controlled by mutp53 and p63 are different. Using TFBS analysis and de novo motif discovery, a p53/p63 decamer site was indeed recovered in loci bound by p63 alone and mutp53/p63, but not in those bound by mutp53. Rather, ther sites for TFs are statistically enriched, many of known growth controlling TFs. These data indicate that the impact of mutp53 is in part through p63 DNA-binding, but for mostly exerted indirectly, by association with different growth controlling TFs.