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Impaired histone inheritance promotes tumor progression
Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact o...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257670/ https://www.ncbi.nlm.nih.gov/pubmed/37301892 http://dx.doi.org/10.1038/s41467-023-39185-y |
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author | Tian, Congcong Zhou, Jiaqi Li, Xinran Gao, Yuan Wen, Qing Kang, Xing Wang, Nan Yao, Yuan Jiang, Jiuhang Song, Guibing Zhang, Tianjun Hu, Suili Liao, JingYi Yu, Chuanhe Wang, Zhiquan Liu, Xiangyu Pei, Xinhai Chan, Kuiming Liu, Zichuan Gan, Haiyun |
author_facet | Tian, Congcong Zhou, Jiaqi Li, Xinran Gao, Yuan Wen, Qing Kang, Xing Wang, Nan Yao, Yuan Jiang, Jiuhang Song, Guibing Zhang, Tianjun Hu, Suili Liao, JingYi Yu, Chuanhe Wang, Zhiquan Liu, Xiangyu Pei, Xinhai Chan, Kuiming Liu, Zichuan Gan, Haiyun |
author_sort | Tian, Congcong |
collection | PubMed |
description | Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression. |
format | Online Article Text |
id | pubmed-10257670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102576702023-06-12 Impaired histone inheritance promotes tumor progression Tian, Congcong Zhou, Jiaqi Li, Xinran Gao, Yuan Wen, Qing Kang, Xing Wang, Nan Yao, Yuan Jiang, Jiuhang Song, Guibing Zhang, Tianjun Hu, Suili Liao, JingYi Yu, Chuanhe Wang, Zhiquan Liu, Xiangyu Pei, Xinhai Chan, Kuiming Liu, Zichuan Gan, Haiyun Nat Commun Article Faithful inheritance of parental histones is essential to maintain epigenetic information and cellular identity during cell division. Parental histones are evenly deposited onto the replicating DNA of sister chromatids in a process dependent on the MCM2 subunit of DNA helicase. However, the impact of aberrant parental histone partition on human disease such as cancer is largely unknown. In this study, we construct a model of impaired histone inheritance by introducing MCM2-2A mutation (defective in parental histone binding) in MCF-7 breast cancer cells. The resulting impaired histone inheritance reprograms the histone modification landscapes of progeny cells, especially the repressive histone mark H3K27me3. Lower H3K27me3 levels derepress the expression of genes associated with development, cell proliferation, and epithelial to mesenchymal transition. These epigenetic changes confer fitness advantages to some newly emerged subclones and consequently promote tumor growth and metastasis after orthotopic implantation. In summary, our results indicate that impaired inheritance of parental histones can drive tumor progression. Nature Publishing Group UK 2023-06-10 /pmc/articles/PMC10257670/ /pubmed/37301892 http://dx.doi.org/10.1038/s41467-023-39185-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tian, Congcong Zhou, Jiaqi Li, Xinran Gao, Yuan Wen, Qing Kang, Xing Wang, Nan Yao, Yuan Jiang, Jiuhang Song, Guibing Zhang, Tianjun Hu, Suili Liao, JingYi Yu, Chuanhe Wang, Zhiquan Liu, Xiangyu Pei, Xinhai Chan, Kuiming Liu, Zichuan Gan, Haiyun Impaired histone inheritance promotes tumor progression |
title | Impaired histone inheritance promotes tumor progression |
title_full | Impaired histone inheritance promotes tumor progression |
title_fullStr | Impaired histone inheritance promotes tumor progression |
title_full_unstemmed | Impaired histone inheritance promotes tumor progression |
title_short | Impaired histone inheritance promotes tumor progression |
title_sort | impaired histone inheritance promotes tumor progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257670/ https://www.ncbi.nlm.nih.gov/pubmed/37301892 http://dx.doi.org/10.1038/s41467-023-39185-y |
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