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P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …