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

Wen, Qing, Zhou, Jiaqi, Tian, Congcong, Li, Xinran, Song, Guibing, Gao, Yuan, Sun, Yaping, Ma, Chiyuan, Yao, Sitong, Liang, Xiaoyan, Kang, Xing, Wang, Nan, Yao, Yuan, Wang, Hongbao, Liang, Xiaohuan, Tang, Jialin, Offer, Steven M, Lei, Xiaohua, Yu, Chuanhe, Liu, Xiangyu, Liu, Zichuan, Wang, Zhiquan, Gan, Haiyun (September 2023) Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation. Nature Genetics, 55 (9). pp. 1555-1566. ISSN 1061-4036

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell differentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > helicase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:	Gao, Yuan
Communities:	CSHL labs > Vakoc lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	September 2023
Date Deposited:	23 Jan 2024 20:52
Last Modified:	23 Jan 2024 20:52
PMCID:	PMC10777717
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41419

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