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:
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:
URI: https://repository.cshl.edu/id/eprint/41419

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