(A) A screenshot of chromosome 3 using UCSC genome browser shows similar DNA-binding profiles from our ChIP-seq analysis of two normal human primary keratinocyte cell lines (wt1 and wt2) with two different antibodies (4A4, pan-p63 and H129, α-specific). The p63 binding sites analyzed with MACS [35] using P value 1×10−9 are shown in red, and previously reported p63 binding sites in ChIP-on-chip analysis [17] are shown in black. (B) The p63 motif was identified by a de novo motif analysis (see Materials and Methods). Based on a previously developed p53scan algorithm [37] with this newly identified p63 Positional Weight Matrix (PWM), p63scan was developed. (C) The performance of p63scan using the de novo identified motif shows superior sensitivity compared to previously reported p63MH without compromising specificity. (D) Distribution of the p63-binding site location relative to RefSeq genes. Locations of binding sites are divided into: TSS flanking region (5 kb upstream of TSS, first exon and first intron), intragenic region (all introns and exons except first), <25 kb (5–25 kb upstream or 25 kb downstream of last exon), or intergenic regions (everything else). The asterisk represents significant enrichment.