ArticleScience advances2025
Disabling leading and lagging strand histone transmission results in parental histones loss and reduced cell plasticity and viability.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation.PLoS genetics · 2026Article
- In vitro reconstitution of chromatin replication recapitulates symmetric histone recycling.Nature communications · 2026Article
- Epigenetic maintenance of PRC2-repressed chromatin requires RTT109 but not H3K56 acetylation.bioRxiv : the preprint server for biology · 2026Article
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- Histone supply: a precious commodity for cell identity.The Biochemical journal · 2025Review
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Authors and funding
9 authors.
Funding
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Abstract
In the process of DNA replication, the first steps in restoring the chromatin landscape involve parental histone recycling and new histone deposition. Disrupting histone recycling to either the leading or lagging strand induces asymmetric histone inheritance, affecting epigenome maintenance and cellular identity. However, the order and kinetics of these effects remain elusive. Here, we use inducible mutants to dissect the early and late consequences of impaired histone recycling. Simultaneous disruption of both leading (POLE4) and lagging strand (MCM2-2A) recycling pathways impairs the transmission of parental histones to newly synthesized DNA, releasing some parental histones to the soluble pool. Subsequently, H3K27me3 accumulates aberrantly during chromatin restoration in a manner preceding gene expression changes. Loss of histone inheritance and the ensuing chromatin restoration defects alter gene expression in embryonic stem cells and challenge differentiation programs and cell viability. Our findings demonstrate the importance of efficient transmission of histone-based information during DNA replication for maintaining chromatin landscapes, differentiation potential, and cellular viability.
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