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

Karsli Uzunbas G, Ahmed F, Sammons MA . bioRxiv


Transcriptional activation by p53 provides powerful, organism-wide tumor suppression. 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 the p53 family member 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.