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Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, gene...

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Autores principales: Britton, Edward, Rogerson, Connor, Mehta, Shaveta, Li, Yaoyong, Li, Xiaodun, Fitzgerald, Rebecca C., Ang, Yeng S., Sharrocks, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578490/
https://www.ncbi.nlm.nih.gov/pubmed/28859074
http://dx.doi.org/10.1371/journal.pgen.1006879
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author Britton, Edward
Rogerson, Connor
Mehta, Shaveta
Li, Yaoyong
Li, Xiaodun
Fitzgerald, Rebecca C.
Ang, Yeng S.
Sharrocks, Andrew D.
author_facet Britton, Edward
Rogerson, Connor
Mehta, Shaveta
Li, Yaoyong
Li, Xiaodun
Fitzgerald, Rebecca C.
Ang, Yeng S.
Sharrocks, Andrew D.
author_sort Britton, Edward
collection PubMed
description Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells.
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spelling pubmed-55784902017-09-15 Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma Britton, Edward Rogerson, Connor Mehta, Shaveta Li, Yaoyong Li, Xiaodun Fitzgerald, Rebecca C. Ang, Yeng S. Sharrocks, Andrew D. PLoS Genet Research Article Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells. Public Library of Science 2017-08-31 /pmc/articles/PMC5578490/ /pubmed/28859074 http://dx.doi.org/10.1371/journal.pgen.1006879 Text en © 2017 Britton et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Britton, Edward
Rogerson, Connor
Mehta, Shaveta
Li, Yaoyong
Li, Xiaodun
Fitzgerald, Rebecca C.
Ang, Yeng S.
Sharrocks, Andrew D.
Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
title Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
title_full Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
title_fullStr Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
title_full_unstemmed Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
title_short Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma
title_sort open chromatin profiling identifies ap1 as a transcriptional regulator in oesophageal adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578490/
https://www.ncbi.nlm.nih.gov/pubmed/28859074
http://dx.doi.org/10.1371/journal.pgen.1006879
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