Distinct p53 genomic binding patterns in normal and cancer-derived human cells

Botcheva, K., McCorkle, S. R., McCombie, W. R., Dunn, J. J., Anderson, C. W. (2011) Distinct p53 genomic binding patterns in normal and cancer-derived human cells. Cell Cycle, 10 (24). pp. 4237-4249. ISSN 1538-4101

URL: http://www.ncbi.nlm.nih.gov/pubmed/22127205
DOI: 10.4161/cc.10.24.18383

Abstract

We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIP-seq peaks to the recently published IMR90 methylome(1) and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

Item Type: Paper
Uncontrolled Keywords: p53 whole genome binding tumor suppressor transcription factor CpG island ChIP-seq tumor-suppressor protein messenger-rna decay dna methylation cpg islands bidirectional promoters p53-responsive genes p53-binding sites noncoding rnas core promoter target genes
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL labs > McCombie lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: Matt Covey
Date Deposited: 06 Feb 2013 16:11
Last Modified: 13 Oct 2015 19:31
PMCID: PMC3272258
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27168

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