Data from Genome-wide p63-Target Gene Analyses Reveal TAp63/NRF2-Dependent Oxidative Stress Responses

• DOI: 10.1158/2767-9764.c.7054670.v1
• Publication Date: 2024-02-01T14:20:46Z
• Authors: Marco Napoli; Avani A. Deshpande; Deepavali Chakrav...; Kimal Rajapakshe; Preethi H. Gunaratne; Cristian Coarfa; Elsa R. Flores

<div>Abstract<p>The p53 family member <i>TP63</i> encodes two sets of N-terminal isoforms, TAp63 and ΔNp63 isoforms. They each regulate diverse biological functions in epidermal morphogenesis cancer. In the skin, where their activities have been extensively characterized, prevents premature aging by regulating quiescence genomic stability stem cells required for wound healing hair regeneration, while controls maintenance terminal differentiation basal cells. This functional diversity is surprising given that these isoforms share a high degree similarity, including an identical sequence DNA-binding domain. To understand mechanisms transcriptional programs regulated p63 isoform leading to functions, we performed genome-wide analyses using isoform-specific chromatin immunoprecipitation, RNA sequencing, metabolomics <i>TAp63<sup>−</sup><sup>/</sup><sup>−</sup></i> <i>ΔNp63<sup>−</sup><sup>/</sup><sup>−</sup></i> mouse Our data indicate physically functionally interact with distinct transcription factors downstream regulation target genes, thus ultimately unique processes. findings unveil novel transcriptomes control cooperation between NRF2 modulation metabolic pathways response oxidative stress providing mechanistic explanation <i>TAp63</i> knock out phenotypes.</p>Significance:<p>The ΔNp63, epithelial tumorigenesis through interaction subsequent programs.</p></div>