The p53 transcriptional response across tumor types reveals core and outcome-specific signatures modulated by cis-regulatory lncRNAs [RNA-seq]

The p53 pathway is a universal tumor suppressor mechanism but the differences of the p53 transcriptional response to oncogenic stress across different tumor types are poorly understood. Using a panel of murine cancer cell lines, we observed that the majority of p53-bound sites were tumor type-specific. Analysis of common p53 targets defined a small but robust core signature and revealed a senescence-specific repression geneset. Characterization of novel transcripts identified p53-induced lncRNAs, which frequently associated with chromatin and regulated their neighboring mRNAs. These findings shed light on the unique and shared p53 transcriptional signatures across different contexts and clarify the contributions of lncRNAs to the p53 transcriptome. Overall design: RNA seq of K-rasG12D; p53LSL/LSL; Rosa26-CreERT2 (KPR) cell lines isolated from murine lung adenocarcinomas (LA), sarcomas (SA), and lymphomas (LY)