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Identification of universal and cell-type specific p53 DNA binding
BACKGROUND: The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 bi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027055/ https://www.ncbi.nlm.nih.gov/pubmed/32070277 http://dx.doi.org/10.1186/s12860-020-00251-8 |
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author | Hafner, Antonina Kublo, Lyubov Tsabar, Michael Lahav, Galit Stewart-Ornstein, Jacob |
author_facet | Hafner, Antonina Kublo, Lyubov Tsabar, Michael Lahav, Galit Stewart-Ornstein, Jacob |
author_sort | Hafner, Antonina |
collection | PubMed |
description | BACKGROUND: The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 binding and thus question the selective and cell-type dependent function of p53. RESULTS: To systematically assess the cell-type specificity of p53, we measured its association with DNA in 12 p53 wild-type cancer cell lines, from a range of epithelial linages, in response to ionizing radiation. We found that the majority of bound sites were occupied across all cell lines, however we also identified a subset of binding sites that were specific to one or a few cell lines. Unlike the shared p53-bound genome, which was not dependent on chromatin accessibility, the association of p53 with these atypical binding sites was well explained by chromatin accessibility and could be modulated by forcing cell state changes such as the epithelial-to-mesenchymal transition. CONCLUSIONS: Our study reconciles previous conflicting views in the p53 field, by demonstrating that although the majority of p53 DNA binding is conserved across cell types, there is a small set of cell line specific binding sites that depend on cell state. |
format | Online Article Text |
id | pubmed-7027055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70270552020-02-25 Identification of universal and cell-type specific p53 DNA binding Hafner, Antonina Kublo, Lyubov Tsabar, Michael Lahav, Galit Stewart-Ornstein, Jacob BMC Mol Cell Biol Research Article BACKGROUND: The tumor suppressor p53 is a major regulator of the DNA damage response and has been suggested to selectively bind and activate cell-type specific gene expression programs. However recent studies and meta-analyses of genomic data propose largely uniform, and condition independent p53 binding and thus question the selective and cell-type dependent function of p53. RESULTS: To systematically assess the cell-type specificity of p53, we measured its association with DNA in 12 p53 wild-type cancer cell lines, from a range of epithelial linages, in response to ionizing radiation. We found that the majority of bound sites were occupied across all cell lines, however we also identified a subset of binding sites that were specific to one or a few cell lines. Unlike the shared p53-bound genome, which was not dependent on chromatin accessibility, the association of p53 with these atypical binding sites was well explained by chromatin accessibility and could be modulated by forcing cell state changes such as the epithelial-to-mesenchymal transition. CONCLUSIONS: Our study reconciles previous conflicting views in the p53 field, by demonstrating that although the majority of p53 DNA binding is conserved across cell types, there is a small set of cell line specific binding sites that depend on cell state. BioMed Central 2020-02-18 /pmc/articles/PMC7027055/ /pubmed/32070277 http://dx.doi.org/10.1186/s12860-020-00251-8 Text en © The Author(s) 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Hafner, Antonina Kublo, Lyubov Tsabar, Michael Lahav, Galit Stewart-Ornstein, Jacob Identification of universal and cell-type specific p53 DNA binding |
title | Identification of universal and cell-type specific p53 DNA binding |
title_full | Identification of universal and cell-type specific p53 DNA binding |
title_fullStr | Identification of universal and cell-type specific p53 DNA binding |
title_full_unstemmed | Identification of universal and cell-type specific p53 DNA binding |
title_short | Identification of universal and cell-type specific p53 DNA binding |
title_sort | identification of universal and cell-type specific p53 dna binding |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027055/ https://www.ncbi.nlm.nih.gov/pubmed/32070277 http://dx.doi.org/10.1186/s12860-020-00251-8 |
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