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

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 ChIPseq peaks to the recently published IMR90 methylome1 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 p53more » binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE SC OFFICE OF SCIENCE (SC)
OSTI Identifier:
1041595
Report Number(s):
BNL-96203-2011-JA
Journal ID: ISSN 1538-4101; R&D Project: BO-129; KP1602020; TRN: US201212%%13
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Cell Cycle
Additional Journal Information:
Journal Volume: 10; Journal Issue: 24; Journal ID: ISSN 1538-4101
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANIMAL CELLS; AVAILABILITY; CHROMATIN; DISTRIBUTION; DNA; FIBROBLASTS; NEOPLASMS; TRANSCRIPTION; p53; whole genome binding; tumor suppressor; transcription factor; CpG island; ChIP-seq

Citation Formats

Botcheva, K, R, McCorkle S, R, McCombie W, J, Dunn J, and W, Anderson C. Distinct p53 genomic binding patterns in normal and cancer-derived human cells. United States: N. p., 2011. Web. doi:10.4161/cc.10.24.18383.
Botcheva, K, R, McCorkle S, R, McCombie W, J, Dunn J, & W, Anderson C. Distinct p53 genomic binding patterns in normal and cancer-derived human cells. United States. https://doi.org/10.4161/cc.10.24.18383
Botcheva, K, R, McCorkle S, R, McCombie W, J, Dunn J, and W, Anderson C. 2011. "Distinct p53 genomic binding patterns in normal and cancer-derived human cells". United States. https://doi.org/10.4161/cc.10.24.18383.
@article{osti_1041595,
title = {Distinct p53 genomic binding patterns in normal and cancer-derived human cells},
author = {Botcheva, K and R, McCorkle S and R, McCombie W and J, Dunn J and W, Anderson C},
abstractNote = {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 ChIPseq peaks to the recently published IMR90 methylome1 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.},
doi = {10.4161/cc.10.24.18383},
url = {https://www.osti.gov/biblio/1041595}, journal = {Cell Cycle},
issn = {1538-4101},
number = 24,
volume = 10,
place = {United States},
year = {Thu Dec 15 00:00:00 EST 2011},
month = {Thu Dec 15 00:00:00 EST 2011}
}