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Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.

Younger ST, Kenzelmann-Broz D, Jung H, Attardi LD, Rinn JL - Nucleic Acids Res. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

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p53 regulation occurs predominantly within enhancer-like regions in primary mouse embryonic fibroblasts. (A) Enrichment analysis of p53 binding sites within modified chromatin across several mouse cell types. (B) Enrichment analysis of transcription factor co-occurrence with p53 binding sites across several mouse cell types.
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Figure 7: p53 regulation occurs predominantly within enhancer-like regions in primary mouse embryonic fibroblasts. (A) Enrichment analysis of p53 binding sites within modified chromatin across several mouse cell types. (B) Enrichment analysis of transcription factor co-occurrence with p53 binding sites across several mouse cell types.

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.


Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.

Younger ST, Kenzelmann-Broz D, Jung H, Attardi LD, Rinn JL - Nucleic Acids Res. (2015)

p53 regulation occurs predominantly within enhancer-like regions in primary mouse embryonic fibroblasts. (A) Enrichment analysis of p53 binding sites within modified chromatin across several mouse cell types. (B) Enrichment analysis of transcription factor co-occurrence with p53 binding sites across several mouse cell types.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482066&req=5

Figure 7: p53 regulation occurs predominantly within enhancer-like regions in primary mouse embryonic fibroblasts. (A) Enrichment analysis of p53 binding sites within modified chromatin across several mouse cell types. (B) Enrichment analysis of transcription factor co-occurrence with p53 binding sites across several mouse cell types.
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.

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.

View Article: PubMed Central - PubMed

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
Related in: MedlinePlus