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

Nucleic Acids Res
Authors
Keywords
Abstract

The tumor suppressor p53 has been studied extensively as a direct transcriptional activator of protein-coding genes. Recent studies, however, have shed light on novel regulatory functions of p53 within noncoding regions of the genome. 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. Notably, our approach identified conserved features of the p53 network in both human and mouse primary fibroblast models. In addition to known p53 targets, we identify many previously unappreciated mRNAs and long noncoding RNAs that are regulated by p53. Moreover, we find that p53 binding occurs predominantly within enhancers in both human and mouse model systems. 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.

Year of Publication
2015
Journal
Nucleic Acids Res
Volume
43
Issue
9
Pages
4447-62
Date Published
2015 May 19
ISSN
1362-4962
URL
DOI
10.1093/nar/gkv284
PubMed ID
25883152
PubMed Central ID
PMC4482066
Links
Grant list
R01 ES020260 / ES / NIEHS NIH HHS / United States
1DP2OD00667 / OD / NIH HHS / United States
1R01ES020260-01 / ES / NIEHS NIH HHS / United States