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Cited by 211Cancer-related Molecular PathwaysGenomics and Chromatin DynamicsChromatin Remodeling and Cancer

Characterization of genome-wide p53-binding sites upon stress response

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Smeenk, Leonie, van Heeringen, Simon J., Koeppel, Max, van Driel, Marc A., Bartels, Stefanie J. J., Akkers, Robert C., Denissov, Sergei, Stunnenberg, Hendrik G. +1 more·2008·Nucleic Acids Research
DOI 10.1093/nar/gkn232PMC PMC2441782
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Abstract

The tumor suppressor p53 is a sequence-specific transcription factor, which regulates the expression of target genes involved in different stress responses. To understand p53's essential transcriptional functions, unbiased analysis of its DNA-binding repertoire is pivotal. In a genome-wide tiling ChIP-on-chip approach, we have identified and characterized 1546 binding sites of p53 upon Actinomycin D treatment. Among those binding sites were known as well as novel p53 target sites, which included regulatory regions of potentially novel transcripts. Using this collection of genome-wide binding sites, a new high-confidence algorithm was developed, p53scan, to identify the p53 consensus-binding motif. Strikingly, this motif was present in the majority of all bound sequences with 83% of all binding sites containing the motif. In the surrounding sequences of the binding sites, several motifs for potential regulatory cobinders were identified. Finally, we show that the majority of the genome-wide p53 target sites can also be bound by overexpressed p63 and p73 in vivo, suggesting that they can possibly play an important role at p53 binding sites. This emphasizes the possible interplay of p53 and its family members in the context of target gene binding. Our study greatly expands the known, experimentally validated p53 binding site repertoire and serves as a valuable knowledgebase for future research.

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  • p53 has non-cell-autonomous effects in stimulating an anti-tumorigenic microenvironment.

    “recent studies have shown non-cell-autonomous effects of p53 in stimulating an anti-tumorigenic microenvironment [10].”

    From Ligand dependent restoration of human TLR3 signaling and death in p53 mutant cells (2016) · cites this paper as [10]

    The Introduction describes p53-mediated tumor suppression through transcriptional regulation, and the Results mention genes associated with cell–cell signaling. Neither passage addresses p53 stimulating an anti-tumorigenic microenvironment through non-cell-autonomous effects. Searches for the claim’s phrasing and for microenvironment-related terms found no passage establishing that point. (LLM, conf=0.76)

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Authors
Smeenk, L., van Heeringen, S. J., Koeppel, M., van Driel, M. A., Bartels, S. J. J., Akkers, R. C., Denissov, S., Stunnenberg, H. G., & Lohrum, M.
Affiliations
Radboud University Nijmegen (NL)
Corresponding author
Lohrum, Marion
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2008-05-12
Volume
36
Issue
11
Pages
3639-3654
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkn232
PMC
PMC2441782
OpenAlex
W2133373613
Cited by
211
References
5
Citations by year
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FWCI
10.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (846.05.002)
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, p53 binding sites, stress response, actinomycin D, p63, p73, p53 family, transcriptional regulation, novel transcripts
MeSH terms
Tumor Protein p73, Algorithms, Base Sequence, Binding Sites, Dactinomycin, DNA-Binding Proteins, Humans, Nuclear Proteins, Transcription Factors, Tumor Suppressor Protein p53, Consensus Sequence, Oligonucleotide Array Sequence Analysis, Genomics, Tumor Suppressor Proteins, Cell Line, Tumor, Chromatin Immunoprecipitation, Regulatory Elements, Transcriptional

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