Impaired histone inheritance promotes tumor progression

Congcong Tian; Jiaqi Zhou; Xinran Li; Yuan Gao; Qing Wen; Xing Kang; Nan Wang; Yuan Yao; Jiuhang Jiang; Guibing Song; Tianjun Zhang; Suili Hu; Jing Yi Liao; Chuanhe Yu; Zhiquan Wang; Xiangyu Liu; Xinhai Pei; Kuiming Chan; Zichuan Liu; Haiyun Gan

doi:10.1038/s41467-023-39185-y

Impaired histone inheritance promotes tumor progression

Congcong Tian, Jiaqi Zhou, Xinran Li, Yuan Gao, Qing Wen, Xing Kang, Nan Wang, Yuan Yao, Jiuhang Jiang, Guibing Song, Tianjun Zhang, Suili Hu, Jing Yi Liao, Chuanhe Yu, Zhiquan Wang, Xiangyu Liu, Xinhai Pei, Kuiming Chan, Zichuan Liu, Haiyun Gan

The Hormel Institute

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

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.

Original language	English (US)
Article number	3429
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-39185-y
State	Published - Dec 2023

Bibliographical note

Funding Information:
This work was supported by the following fundings: National Key R&D Program of China (Grant No. 2019YFA0903800 to H.G.), the Major Program of the National Natural Science Foundation of China (32090031 to H.G.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0480000 to H.G.), the General Program of the National Natural Science Foundation of China (32070610 to H.G.), the National Natural Science Foundation of China for Young Scholars (32000580 to Q.W., 32100460 to J.Z. and 32101178 to Y.Y.), the Guangdong Province Fund for Distinguished Young Scholars (2021B1515020109 to H.G.), Guangdong Basic and Applied Basic Research Foundation (2021A1515110377 to X.K.), Shenzhen Institute of Synthetic Biology Scientific Research Program (JCHZ20200005, DWKF20210001, ZTXM20190019 to H.G.), and Project funded by China Postdoctoral Science Foundation (2021M693301 to C.T and 2021M703386 to J.Z.).

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© 2023, The Author(s).

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title = "Impaired histone inheritance promotes tumor progression",

abstract = "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.",

author = "Congcong Tian and Jiaqi Zhou and Xinran Li and Yuan Gao and Qing Wen and Xing Kang and Nan Wang and Yuan Yao and Jiuhang Jiang and Guibing Song and Tianjun Zhang and Suili Hu and Liao, {Jing Yi} and Chuanhe Yu and Zhiquan Wang and Xiangyu Liu and Xinhai Pei and Kuiming Chan and Zichuan Liu and Haiyun Gan",

note = "Funding Information: This work was supported by the following fundings: National Key R&D Program of China (Grant No. 2019YFA0903800 to H.G.), the Major Program of the National Natural Science Foundation of China (32090031 to H.G.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0480000 to H.G.), the General Program of the National Natural Science Foundation of China (32070610 to H.G.), the National Natural Science Foundation of China for Young Scholars (32000580 to Q.W., 32100460 to J.Z. and 32101178 to Y.Y.), the Guangdong Province Fund for Distinguished Young Scholars (2021B1515020109 to H.G.), Guangdong Basic and Applied Basic Research Foundation (2021A1515110377 to X.K.), Shenzhen Institute of Synthetic Biology Scientific Research Program (JCHZ20200005, DWKF20210001, ZTXM20190019 to H.G.), and Project funded by China Postdoctoral Science Foundation (2021M693301 to C.T and 2021M703386 to J.Z.). Publisher Copyright: {\textcopyright} 2023, The Author(s).",

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doi = "10.1038/s41467-023-39185-y",

language = "English (US)",

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AU - Tian, Congcong

AU - Zhou, Jiaqi

AU - Li, Xinran

AU - Gao, Yuan

AU - Wen, Qing

AU - Kang, Xing

AU - Wang, Nan

AU - Yao, Yuan

AU - Jiang, Jiuhang

AU - Song, Guibing

AU - Zhang, Tianjun

AU - Hu, Suili

AU - Liao, Jing Yi

AU - Yu, Chuanhe

AU - Wang, Zhiquan

AU - Liu, Xiangyu

AU - Pei, Xinhai

AU - Chan, Kuiming

AU - Liu, Zichuan

AU - Gan, Haiyun

N1 - Funding Information: This work was supported by the following fundings: National Key R&D Program of China (Grant No. 2019YFA0903800 to H.G.), the Major Program of the National Natural Science Foundation of China (32090031 to H.G.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0480000 to H.G.), the General Program of the National Natural Science Foundation of China (32070610 to H.G.), the National Natural Science Foundation of China for Young Scholars (32000580 to Q.W., 32100460 to J.Z. and 32101178 to Y.Y.), the Guangdong Province Fund for Distinguished Young Scholars (2021B1515020109 to H.G.), Guangdong Basic and Applied Basic Research Foundation (2021A1515110377 to X.K.), Shenzhen Institute of Synthetic Biology Scientific Research Program (JCHZ20200005, DWKF20210001, ZTXM20190019 to H.G.), and Project funded by China Postdoctoral Science Foundation (2021M693301 to C.T and 2021M703386 to J.Z.). Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - 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.

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ER -

Impaired histone inheritance promotes tumor progression

Abstract

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