Journal article
Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation
Nature genetics, Vol.55(9), pp.1555-1566
09/01/2023
DOI: 10.1038/s41588-023-01477-w
PMCID: PMC10777717
PMID: 37666989
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.
Details
- Title: Subtitle
- Symmetric inheritance of parental histones contributes to safeguarding the fate of mouse embryonic stem cells during differentiation
- Creators
- Qing Wen - Shenzhen Institutes of Advanced TechnologyJiaqi Zhou - Shenzhen Institutes of Advanced TechnologyCongcong Tian - Shenzhen Institutes of Advanced TechnologyXinran Li - Shenzhen Institutes of Advanced TechnologyGuibing Song - Northwest A&F UniversityYuan Gao - Cold Spring Harbor LaboratoryYaping Sun - Shenzhen Institutes of Advanced TechnologyChiyuan Ma - Shenzhen Institutes of Advanced TechnologySitong Yao - College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaXiaoyan Liang - Shenzhen Institutes of Advanced TechnologyXing Kang - Shenzhen Institutes of Advanced TechnologyNan Wang - Shenzhen Institutes of Advanced TechnologyYuan Yao - Shenzhen Institutes of Advanced TechnologyHongbao Wang - Northwest A&F UniversityXiaohuan Liang - College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaJialin Tang - Shenzhen University Health Science CenterSteven M Offer - Mayo ClinicXiaohua Lei - Shenzhen Institutes of Advanced TechnologyChuanhe Yu - University of MinnesotaXiangyu Liu - Shenzhen University Health Science CenterZichuan Liu - Tianjin UniversityZhiquan Wang - Mayo ClinicHaiyun Gan - Shenzhen Institutes of Advanced Technology
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.55(9), pp.1555-1566
- DOI
- 10.1038/s41588-023-01477-w
- PMID
- 37666989
- PMCID
- PMC10777717
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Grant note
- R01 GM130588 / NIGMS NIH HHS
- Language
- English
- Date published
- 09/01/2023
- Academic Unit
- Pathology
- Record Identifier
- 9984618630102771
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