Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage
Open accessAbstract
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.
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Long-distance transactivation is mediated by the binding of p53 to enhancers.
“long-distance transactivation is reportedly mediated by the binding of p53 to enhancers.30, 65, 66”
From Census and evaluation of p53 target genes (2017) · cites this paper as [30]
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- Authors
- Younger, S. T., Kenzelmann-Broz, D., Jung, H., Attardi, L. D., & Rinn, J. L.
- Affiliations
- Broad Institute (US)
- Stanford Medicine (US)
- Corresponding author
- Rinn, John L.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-04-16
- Volume
- 43
- Issue
- 9
- Pages
- 4447-4462
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4482066
- OpenAlex
- W1980828363
- Cited by
- 99
- References
- 66
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 15 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 7 · 2017: 16 · 2016: 18 · 2015: 5
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (1DP2OD00667)
- National Institute of Environmental Health Sciences (R01ES020260)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- p53, enhancer regulation, DNA damage response, long non-coding RNA, p53 binding sites, chromatin state, tumor suppressor regulation, fibroblasts
- MeSH terms
- Animals, Cell Line, Cells, Cultured, DNA Damage, Enhancer Elements, Genetic, Fibroblasts, Gene Expression Regulation, Humans, Proteins, Tumor Suppressor Protein p53, Genomics, Mice, RNA, Long Noncoding
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