Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation

Qing Wen; Jiaqi Zhou; Congcong Tian; Xinran Li; Guibing Song; Yuan Gao; Yaping Sun; Chiyuan Ma; Sitong Yao; Xiaoyan Liang; Xing Kang; Nan Wang; Yuan Yao; Hongbao Wang; Xiaohuan Liang; Jialin Tang; Steven M. Offer; Xiaohua Lei; Chuanhe Yu; Xiangyu Liu; Zichuan Liu; Zhiquan Wang; Haiyun Gan

doi:10.1038/s41588-023-01477-w

Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation

Qing Wen, Jiaqi Zhou, Congcong Tian, Xinran Li, Guibing Song, Yuan Gao, Yaping Sun, Chiyuan Ma, Sitong Yao, Xiaoyan Liang, Xing Kang, Nan Wang, Yuan Yao, Hongbao Wang, Xiaohuan Liang, Jialin Tang, Steven M. Offer, Xiaohua Lei, Chuanhe Yu, Xiangyu LiuZichuan Liu, Zhiquan Wang, Haiyun Gan

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

Abstract

Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone propagation remains unclear. Here we show that Mcm2-mutated or Pole3-deleted mouse embryonic stem cells (ESCs) display aberrant histone landscapes and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality. ESCs with biased parental histone transfer exhibit increased epigenetic heterogeneity, showing altered histone variant H3.3 and H3K27me3 patterning at genomic sites regulating differentiation genes. Our results indicate that the lagging strand pattern of H3.3 leads to the redistribution of H3K27me3 in Mcm2-2A ESCs. We demonstrate that symmetric parental histone deposition to sister chromatids contributes to cellular differentiation and development.

Original language	English (US)
Pages (from-to)	1555-1566
Number of pages	12
Journal	Nature Genetics
Volume	55
Issue number	9
DOIs	https://doi.org/10.1038/s41588-023-01477-w
State	Published - Sep 2023

ASJC Scopus subject areas

Genetics

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Wen, Q., Zhou, J., Tian, C., Li, X., Song, G., Gao, Y., Sun, Y., Ma, C., Yao, S., Liang, X., Kang, X., Wang, N., Yao, Y., Wang, H., Liang, X., Tang, J., Offer, S. M., Lei, X., Yu, C., ... Gan, H. (2023). Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation. Nature Genetics, 55(9), 1555-1566. https://doi.org/10.1038/s41588-023-01477-w

Wen, Q, Zhou, J, Tian, C, Li, X, Song, G, Gao, Y, Sun, Y, Ma, C, Yao, S, Liang, X, Kang, X, Wang, N, Yao, Y, Wang, H, Liang, X, Tang, J, Offer, SM, Lei, X, Yu, C, Liu, X, Liu, Z, Wang, Z & Gan, H 2023, 'Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation', Nature Genetics, vol. 55, no. 9, pp. 1555-1566. https://doi.org/10.1038/s41588-023-01477-w

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title = "Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation",

abstract = "Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone propagation remains unclear. Here we show that Mcm2-mutated or Pole3-deleted mouse embryonic stem cells (ESCs) display aberrant histone landscapes and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality. ESCs with biased parental histone transfer exhibit increased epigenetic heterogeneity, showing altered histone variant H3.3 and H3K27me3 patterning at genomic sites regulating differentiation genes. Our results indicate that the lagging strand pattern of H3.3 leads to the redistribution of H3K27me3 in Mcm2-2A ESCs. We demonstrate that symmetric parental histone deposition to sister chromatids contributes to cellular differentiation and development.",

author = "Qing Wen and Jiaqi Zhou and Congcong Tian and Xinran Li and Guibing Song and Yuan Gao and Yaping Sun and Chiyuan Ma and Sitong Yao and Xiaoyan Liang and Xing Kang and Nan Wang and Yuan Yao and Hongbao Wang and Xiaohuan Liang and Jialin Tang and Offer, {Steven M.} and Xiaohua Lei and Chuanhe Yu and Xiangyu Liu and Zichuan Liu and Zhiquan Wang and Haiyun Gan",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

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doi = "10.1038/s41588-023-01477-w",

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AU - Wen, Qing

AU - Zhou, Jiaqi

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AU - Li, Xinran

AU - Song, Guibing

AU - Gao, Yuan

AU - Sun, Yaping

AU - Ma, Chiyuan

AU - Yao, Sitong

AU - Liang, Xiaoyan

AU - Kang, Xing

AU - Wang, Nan

AU - Yao, Yuan

AU - Wang, Hongbao

AU - Liang, Xiaohuan

AU - Tang, Jialin

AU - Offer, Steven M.

AU - Lei, Xiaohua

AU - Yu, Chuanhe

AU - Liu, Xiangyu

AU - Liu, Zichuan

AU - Wang, Zhiquan

AU - Gan, Haiyun

PY - 2023/9

Y1 - 2023/9

N2 - Parental histones, the carriers of posttranslational modifications, are deposited evenly onto the replicating DNA of sister chromatids in a process dependent on the Mcm2 subunit of DNA helicase and the Pole3 subunit of leading-strand DNA polymerase. The biological significance of parental histone propagation remains unclear. Here we show that Mcm2-mutated or Pole3-deleted mouse embryonic stem cells (ESCs) display aberrant histone landscapes and impaired neural differentiation. Mutation of the Mcm2 histone-binding domain causes defects in pre-implantation development and embryonic lethality. ESCs with biased parental histone transfer exhibit increased epigenetic heterogeneity, showing altered histone variant H3.3 and H3K27me3 patterning at genomic sites regulating differentiation genes. Our results indicate that the lagging strand pattern of H3.3 leads to the redistribution of H3K27me3 in Mcm2-2A ESCs. We demonstrate that symmetric parental histone deposition to sister chromatids contributes to cellular differentiation and development.

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Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation

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