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Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes
BACKGROUND: Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. RESULTS: To define alterations in epigenetic landscapes in breast cancers, we...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819162/ https://www.ncbi.nlm.nih.gov/pubmed/29458327 http://dx.doi.org/10.1186/s12864-018-4533-0 |
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author | Xi, Yuanxin Shi, Jiejun Li, Wenqian Tanaka, Kaori Allton, Kendra L. Richardson, Dana Li, Jing Franco, Hector L. Nagari, Anusha Malladi, Venkat S. Coletta, Luis Della Simper, Melissa S. Keyomarsi, Khandan Shen, Jianjun Bedford, Mark T. Shi, Xiaobing Barton, Michelle C. Kraus, W. Lee Li, Wei Dent, Sharon Y. R. |
author_facet | Xi, Yuanxin Shi, Jiejun Li, Wenqian Tanaka, Kaori Allton, Kendra L. Richardson, Dana Li, Jing Franco, Hector L. Nagari, Anusha Malladi, Venkat S. Coletta, Luis Della Simper, Melissa S. Keyomarsi, Khandan Shen, Jianjun Bedford, Mark T. Shi, Xiaobing Barton, Michelle C. Kraus, W. Lee Li, Wei Dent, Sharon Y. R. |
author_sort | Xi, Yuanxin |
collection | PubMed |
description | BACKGROUND: Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. RESULTS: To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. DISCUSSION: Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. CONCLUSIONS: Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4533-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5819162 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58191622018-02-21 Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes Xi, Yuanxin Shi, Jiejun Li, Wenqian Tanaka, Kaori Allton, Kendra L. Richardson, Dana Li, Jing Franco, Hector L. Nagari, Anusha Malladi, Venkat S. Coletta, Luis Della Simper, Melissa S. Keyomarsi, Khandan Shen, Jianjun Bedford, Mark T. Shi, Xiaobing Barton, Michelle C. Kraus, W. Lee Li, Wei Dent, Sharon Y. R. BMC Genomics Research Article BACKGROUND: Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. RESULTS: To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. DISCUSSION: Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. CONCLUSIONS: Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-4533-0) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-20 /pmc/articles/PMC5819162/ /pubmed/29458327 http://dx.doi.org/10.1186/s12864-018-4533-0 Text en © The Author(s). 2018 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 Xi, Yuanxin Shi, Jiejun Li, Wenqian Tanaka, Kaori Allton, Kendra L. Richardson, Dana Li, Jing Franco, Hector L. Nagari, Anusha Malladi, Venkat S. Coletta, Luis Della Simper, Melissa S. Keyomarsi, Khandan Shen, Jianjun Bedford, Mark T. Shi, Xiaobing Barton, Michelle C. Kraus, W. Lee Li, Wei Dent, Sharon Y. R. Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
title | Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
title_full | Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
title_fullStr | Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
title_full_unstemmed | Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
title_short | Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
title_sort | histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819162/ https://www.ncbi.nlm.nih.gov/pubmed/29458327 http://dx.doi.org/10.1186/s12864-018-4533-0 |
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