Symmetric inheritance of parental histones governs epigenome maintenance and embryonic stem cell identity.

Wenger, Alice, Alva Biran, Nicolas Alcaraz, Alba Redó-Riveiro, Annika Charlotte Sell, Robert Krautz, Valentin Flury, et al. 2023. “Symmetric Inheritance of Parental Histones Governs Epigenome Maintenance and Embryonic Stem Cell Identity.”. Nature Genetics 55 (9): 1567-78.

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Abstract

Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome and cell identity remains unknown. Here we show that transmission of histone-based information during DNA replication maintains epigenome fidelity and embryonic stem cell plasticity. Asymmetric segregation of parental histones H3-H4 in MCM2-2A mutants compromised mitotic inheritance of histone modifications and globally altered the epigenome. This included widespread spurious deposition of repressive modifications, suggesting elevated epigenetic noise. Moreover, H3K9me3 loss at repeats caused derepression and H3K27me3 redistribution across bivalent promoters correlated with misexpression of developmental genes. MCM2-2A mutation challenged dynamic transitions in cellular states across the cell cycle, enhancing naïve pluripotency and reducing lineage priming in G1. Furthermore, developmental competence was diminished, correlating with impaired exit from pluripotency. Collectively, this argues that epigenetic inheritance of histone modifications maintains a correctly balanced and dynamic chromatin landscape able to support mammalian cell differentiation.

Last updated on 08/28/2025
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OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations.
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Publisher's Version

OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations.
METHODS: Children (9-12 years) completed a randomized crossover experiment. During two visits, children ate a preload and then snacks ad libitum while watching television, embedded with food or non-food advertisements to assess eating in the absence of hunger (EAH). Primary exposures were obesity-associated genotypes, FTO rs9939609 and MC4R rs571312, and a paediatric-specific polygenic risk score (PRS). Outcomes included consumption of all snacks (total EAH) and gummy candy only (gummy candy EAH). Linear mixed-effects models tested whether genetic exposures related to EAH outcomes. We tested for effect modification by food cues using multiplicative interaction terms.
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