Cell type-dependent control of enhancer and p53 transcriptional activity by p63

In this work, we demonstrate that the p53-induced transcriptome is dependent on pre-establishment of cell type-dependent cis-regulatory networks. The epithelial-specific p53 transcriptome is strongly dependent on p63, which acts as a pioneer factor for epithelial-specific enhancers. These results suggest a broad mechanism for regulating the p53-dependent cellular response to stress through differential regulation of cis-regulatory elements and identify p63 as a direct and critical regulator of enhancer activity in epithelial cell types. Overall design: p53 transcriptome: RNA-Seq and ChIP-Seq