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Title: Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats

Journal Article · · PLoS ONE
 [1];  [2]
  1. Brookhaven National Lab. (BNL), Upton, NY (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States)

The p53 ability to elicit stress specific and cell type specific responses is well recognized, but how that specificity is established remains to be defined. Whether upon activation p53 binds to its genomic targets in a cell type and stress type dependent manner is still an open question. Here we show that the p53 binding to the human genome is selective and cell context-dependent. We mapped the genomic binding sites for the endogenous wild type p53 protein in the human cancer cell line HCT116 and compared them to those we previously determined in the normal cell line IMR90. We report distinct p53 genome-wide binding landscapes in two different cell lines, analyzed under the same treatment and experimental conditions, using the same ChIP-seq approach. This is evidence for cell context dependent p53 genomic binding. The observed differences affect the p53 binding sites distribution with respect to major genomic and epigenomic elements (promoter regions, CpG islands and repeats). We correlated the high-confidence p53 ChIP-seq peaks positions with the annotated human repeats (UCSC Human Genome Browser) and observed both common and cell line specific trends. In HCT116, the p53 binding was specifically enriched at LINE repeats, compared to IMR90 cells. The p53 genome-wide binding patterns in HCT116 and IMR90 likely reflect the different epigenetic landscapes in these two cell lines, resulting from cancer-associated changes (accumulated in HCT116) superimposed on tissue specific differences (HCT116 has epithelial, while IMR90 has mesenchymal origin). In conclusion, our data support the model for p53 binding to the human genome in a highly selective manner, mobilizing distinct sets of genes, contributing to distinct pathways.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-98CH10886
OSTI ID:
1255533
Journal Information:
PLoS ONE, Vol. 9, Issue 11; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 18 works
Citation information provided by
Web of Science

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Cited By (9)

detectMITE: A novel approach to detect miniature inverted repeat transposable elements in genomes journal January 2016
p53 binding sites in normal and cancer cells are characterized by distinct chromatin context journal September 2017
Revealing a human p53 universe journal August 2018
Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic journal May 2016
p53 binding sites in normal and cancer cells are characterized by distinct chromatin context posted_content February 2017
Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage journal May 2017
High-Resolution 4C Reveals Rapid p53-Dependent Chromatin Reorganization of the CDKN1A Locus in Response to Stress journal October 2016
p53 binding to human genome: crowd control navigation in chromatin context journal December 2014
Identification and Analysis of P53-Mediated Competing Endogenous RNA Network in Human Hepatocellular Carcinoma journal January 2017

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