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 journalArticlepeer-review

7 Scopus citations

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 languageEnglish (US)
Pages (from-to)1555-1566
Number of pages12
JournalNature Genetics
Volume55
Issue number9
DOIs
StatePublished - Sep 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

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