Global genomic profiling of p53-regulated genes

p53 is a critical tumor suppressor and works as a stress-induced transcription factor to induce target genes mediating apoptosis, cell cycle arrest and senescence or other responses. To gain new insights into p53 biology, we used high-throughput sequencing to analyze global p53 transcriptional networks in primary mouse embryo fibroblasts in response to DNA damage. ChIP-sequencing reveals 4785 p53-bound sites in the genome located near 3193 genes involved in diverse biological processes. RNA-sequencing analysis shows that only a subset of p53-bound genes is transcriptionally regulated, yielding a list of 432 p53-bound and regulated genes. Furthermore, we define a list of 1269 basal-p53 regulated genes, of which 253 are p53-bound and basal-p53 regulated. Overall design: ChIP-seq was performed to determine the genome-wide p53 binding sites in doxorubicin-treated primary MEFs. RNA-seq was used to define differentially expressed genes in response to DNA damage in wild-type and p53-/- MEFs, and basal p53 regulated genes by deriving differentially expressed genes between untreated wild-type and p53-/- MEFs.