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Title: 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 » 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.« less

Authors:
 [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)
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:
Journal Article: 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. 2014. "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},
url = {https://www.osti.gov/biblio/1255533}, journal = {PLoS ONE},
issn = {1932-6203},
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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Cited by: 18 works
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Works referenced in this record:

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The first 30 years of p53: growing ever more complex
journal, October 2009


Transcriptional control of human p53-regulated genes
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Divergent Evolution of Human p53 Binding Sites: Cell Cycle Versus Apoptosis
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Characterization of genome-wide p53-binding sites upon stress response
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A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection
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Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells
journal, June 2013


Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis
journal, July 2012


Distinct p53 genomic binding patterns in normal and cancer-derived human cells
journal, December 2011


p53 functions and cell lines: Have we learned the lessons from the past?
journal, April 2010


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journal, January 2009


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journal, June 2002


Genome-wide profiling reveals stimulus-specific functions of p53 during differentiation and DNA damage of human embryonic stem cells
journal, September 2013


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journal, March 2011


Repetitive Elements May Comprise Over Two-Thirds of the Human Genome
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Methylation and deamination of CpGs generate p53-binding sites on a genomic scale
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Impact of Alu repeats on the evolution of human p53 binding sites
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Dissimilar DNA binding by p53 in normal and tumor-derived cells
journal, December 2011


p53 cooperates with DNA methylation and a suicidal interferon response to maintain epigenetic silencing of repeats and noncoding RNAs
journal, December 2012


The Maintenance of Epigenetic States by p53: The Guardian of the Epigenome
journal, December 2012


Hypomethylation distinguishes genes of some human cancers from their normal counterparts
journal, January 1983


Increased methylation variation in epigenetic domains across cancer types
journal, June 2011


LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer
journal, January 2008


MEME SUITE: tools for motif discovery and searching
journal, May 2009


Inferring direct DNA binding from ChIP-seq
journal, May 2012


Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
journal, December 2008


Blinded by the Light: The Growing Complexity of p53
journal, May 2009


DREME: motif discovery in transcription factor ChIP-seq data
journal, May 2011


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journal, January 2007


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journal, April 2011


LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer
journal, January 2008


Transcription Factor Target Practice
journal, January 2006


A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection
journal, October 2013


Methylation and deamination of CpGs generate p53-binding sites on a genomic scale
journal, February 2009


An integrated map of p53-binding sites and histone modification in the human ENCODE regions
journal, February 2007


PUMA Induces the Rapid Apoptosis of Colorectal Cancer Cells
journal, March 2001


PUMA, a Novel Proapoptotic Gene, Is Induced by p53
journal, March 2001


Hypomethylation distinguishes genes of some human cancers from their normal counterparts
journal, January 1983


Insights into p53 transcriptional function via genome-wide chromatin occupancy and gene expression analysis
journal, July 2012


Mapping and analysis of chromatin state dynamics in nine human cell types
journal, March 2011


Definition of a consensus binding site for p53
journal, April 1992


Computation for ChIP-seq and RNA-seq studies
journal, October 2009


Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
journal, December 2008


The first 30 years of p53: growing ever more complex
journal, October 2009


Transcriptional control of human p53-regulated genes
journal, May 2008


p53 responsive elements in human retrotransposons
journal, August 2009


Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53
journal, November 2007


Mapping accessible chromatin regions using Sono-Seq
journal, August 2009


p53 cooperates with DNA methylation and a suicidal interferon response to maintain epigenetic silencing of repeats and noncoding RNAs
journal, December 2012


Defining functional DNA elements in the human genome
journal, April 2014


The p53MH algorithm and its application in detecting p53-responsive genes
journal, June 2002


DREME: motif discovery in transcription factor ChIP-seq data
journal, May 2011


Characterization of genome-wide p53-binding sites upon stress response
journal, May 2008


MEME SUITE: tools for motif discovery and searching
journal, May 2009


Inferring direct DNA binding from ChIP-seq
journal, May 2012


Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells
journal, June 2013


Genome-wide profiling reveals stimulus-specific functions of p53 during differentiation and DNA damage of human embryonic stem cells
journal, September 2013


Functional Analysis of p53 Binding under Differential Stresses
journal, October 2006


Chromatin Immunoprecipitation-Based Screen To Identify Functional Genomic Binding Sites for Sequence-Specific Transactivators
journal, November 2005


Repbase Update, a database of eukaryotic repetitive elements
journal, January 2005


Impact of Alu repeats on the evolution of human p53 binding sites
journal, January 2011


Divergent Evolution of Human p53 Binding Sites: Cell Cycle Versus Apoptosis
journal, January 2005


Repetitive Elements May Comprise Over Two-Thirds of the Human Genome
journal, December 2011


Inherent Signals in Sequencing-Based Chromatin-ImmunoPrecipitation Control Libraries
journal, April 2009


The Maintenance of Epigenetic States by p53: The Guardian of the Epigenome
journal, December 2012


Distinct p53 genomic binding patterns in normal and cancer-derived human cells
journal, December 2011


Works referencing / citing this record:

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


detectMITE: A novel approach to detect miniature inverted repeat transposable elements in genomes
journal, January 2016


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