Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.
Bottom Line: Here, we use a systematic approach that integrates transcriptome-wide expression analysis, genome-wide p53 binding profiles and chromatin state maps to characterize the global regulatory roles of p53 in response to DNA damage.In addition to known p53 targets, we identify many previously unappreciated mRNAs and long noncoding RNAs that are regulated by p53.The ability to modulate enhancer activity offers an additional layer of complexity to the p53 network and greatly expands the diversity of genomic elements directly regulated by p53.
Affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.Show MeSH
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Mentions: We intersected our experimentally determined p53 binding sites from MEFs with the LICR histone ChIP-Seq profiles and found that, similar to human cells, p53 binding occurs most frequently within enhancer (H3K4me1) regions (Figure 7A). Furthermore, enrichment of binding sites within enhancers is comparable to active promoters (H3K4me3 and H3K9ac). Binding sites are most highly enriched within general regulatory regions (H3K27ac), which are inclusive of both active promoters and enhancers. Conversely, enrichment of binding sites within regions of repressed chromatin (H3K27me3) and gene bodies (H3K36me3) was not significant. Collectively, these findings suggest that the prevalence of enhancer recognition by p53 is conserved across mammals.
Affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.