Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats
Abstract
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-widemore »
- Authors:
-
- Brookhaven National Lab. (BNL), Upton, NY (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1255533
- Grant/Contract Number:
- AC02-98CH10886
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 9; Journal Issue: 11; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Botcheva, Krassimira, and McCorkle, Sean R. Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats. United States: N. p., 2014.
Web. doi:10.1371/journal.pone.0113492.
Botcheva, Krassimira, & McCorkle, Sean R. Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats. United States. https://doi.org/10.1371/journal.pone.0113492
Botcheva, Krassimira, and McCorkle, Sean R. Fri .
"Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats". United States. https://doi.org/10.1371/journal.pone.0113492. https://www.osti.gov/servlets/purl/1255533.
@article{osti_1255533,
title = {Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats},
author = {Botcheva, Krassimira and McCorkle, Sean R.},
abstractNote = {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.},
doi = {10.1371/journal.pone.0113492},
journal = {PLoS ONE},
number = 11,
volume = 9,
place = {United States},
year = {Fri Nov 21 00:00:00 EST 2014},
month = {Fri Nov 21 00:00:00 EST 2014}
}
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Works referencing / citing this record:
detectMITE: A novel approach to detect miniature inverted repeat transposable elements in genomes
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p53 binding sites in normal and cancer cells are characterized by distinct chromatin context
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