Whole-genome cartography of p53 response elements ranked on transactivation potential
Open accessAbstract
BACKGROUND: Many recent studies using ChIP-seq approaches cross-referenced to trascriptome data and also to potentially unbiased in vitro DNA binding selection experiments are detailing with increasing precision the p53-directed gene regulatory network that, nevertheless, is still expanding. However, most experiments have been conducted in established cell lines subjected to specific p53-inducing stimuli, both factors potentially biasing the results. RESULTS: We developed p53retriever, a pattern search algorithm that maps p53 response elements (REs) and ranks them according to predicted transactivation potentials in five classes. Besides canonical, full site REs, we developed specific pattern searches for non-canonical half sites and 3/4 sites and show that they can mediate p53-dependent responsiveness of associated coding sequences. Using ENCODE data, we also mapped p53 REs in about 44,000 distant enhancers and identified a 16-fold enrichment for high activity REs within those sites in the comparison with genomic regions near transcriptional start sites (TSS). Predictions from our pattern search were cross-referenced to ChIP-seq, ChIP-exo, expression, and various literature data sources. Based on the mapping of predicted functional REs near TSS, we examined expression changes of thirteen genes as a function of different p53-inducing conditions, providing further evidence for PDE2A, GAS6, E2F7, APOBEC3H, KCTD1, TRIM32, DICER, HRAS, KITLG and TGFA p53-dependent regulation, while MAP2K3, DNAJA1 and potentially YAP1 were identified as new direct p53 target genes. CONCLUSIONS: We provide a comprehensive annotation of canonical and non-canonical p53 REs in the human genome, ranked on predicted transactivation potential. We also establish or corroborate direct p53 transcriptional control of thirteen genes. The entire list of identified and functionally classified p53 REs near all UCSC-annotated genes and within ENCODE mapped enhancer elements is provided. Our approach is distinct from, and complementary to, existing methods designed to identify p53 response elements. p53retriever is available as an R package at: http://tomateba.github.io/p53retriever .
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Results from multiple studies suggest that p53 can bind and transactivate target genes through noncanonical binding sites, particularly through half-sites.
“In addition, results from multiple studies suggest that p53 can bind and transactivate target genes through noncanonical binding sites, particularly through half-sites.22, 54, 55, 56”
From Census and evaluation of p53 target genes (2017) · cites this paper as [56]
Recent approaches to predict functional sites that lead to target gene activation rely on ranking p53 binding sites based on multiple genome-wide data sets.
“To predict functional sites that lead to target gene activation, recent approaches now rely on ranking p53 binding sites based on multiple genome-wide data sets.18, 19, 56”
From Census and evaluation of p53 target genes (2017) · cites this paper as [56]
Functional p53 binding sites consist of two decameric half-sites, and likely do not contain spacers in between.
“Functional p53 binding sites consist of two decameric half-sites, and likely do not contain spacers in between. 19, 56”
From Census and evaluation of p53 target genes (2017) · cites this paper as [56]
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- Authors
- Tebaldi, T., Zaccara, S., Alessandrini, F., Bisio, A., Ciribilli, Y., & Inga, A.
- Affiliations
- University of Trento (IT)
- Corresponding author
- Tebaldi, Toma
- Inga, Alberto
- Venue
- BMC Genomics
- Published
- 2015-06-17
- Volume
- 16
- Issue
- 1
- Pages
- 464-464
- ISSN
- 1471-2164 (ISSN-L)
- PMC
- PMC4470028
- OpenAlex
- W1579358468
- Cited by
- 72
- References
- 68
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 3 · 2019: 8 · 2018: 9 · 2017: 6 · 2016: 7
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Genomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- 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 response elements, p53 transcriptional regulation, enhancers, transcription start sites, p53 target genes, p53-dependent gene expression, pattern search algorithm, ChIP-seq, ChIP-exo
- MeSH terms
- Algorithms, Binding Sites, Doxorubicin, Humans, Imidazoles, Piperazines, Promoter Regions, Genetic, User-Computer Interface, Transcriptional Activation, Genome, Human, Tumor Suppressor Protein p53, Response Elements, Internet, Transcription Initiation Site, Databases, Genetic, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Chromatin Immunoprecipitation, Transcriptome
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