ArticleThe EMBO journal2022
Epigenetic inheritance is gated by naïve pluripotency and Dppa2.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Epigenetic regulation in early embryogenesis: mechanisms, developmental programming, and transgenerational implications.Frontiers in cell and developmental biology · 2026Review
- Antisense transcription can induce expression memory via stable promoter repression.Genome biology · 2025Article
- Review
- DNA methylation shapes the Polycomb landscape during the exit from naive pluripotency.Nature structural & molecular biology · 2025Article
- An epigenetic toolbox for conservation biologists.Evolutionary applications · 2024Article
- Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.Environmental science & technology · 2024Review
- The molecular basis of heterochromatin assembly and epigenetic inheritance.Molecular cell · 2023Review
- H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate.Development (Cambridge, England) · 2022Article
- OCT4 activates a Suv39h1-repressive antisense lncRNA to couple histone H3 Lysine 9 methylation to pluripotency.Nucleic acids research · 2022Article
- Epigenetic inheritance is gated by naïve pluripotency and Dppa2.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Environmental factors can trigger cellular responses that propagate across mitosis or even generations. Perturbations to the epigenome could underpin such acquired changes, however, the extent and contexts in which modified chromatin states confer heritable memory in mammals is unclear. Here, we exploit a precision epigenetic editing strategy and forced Xist activity to programme de novo heterochromatin domains (epialleles) at endogenous loci and track their inheritance in a developmental model. We find that naïve pluripotent phases systematically erase ectopic domains of heterochromatin via active mechanisms, which likely acts as an intergenerational safeguard against transmission of epialleles. Upon lineage specification, however, acquired chromatin states can be probabilistically inherited under selectively favourable conditions, including propagation of p53 silencing through in vivo development. Using genome-wide CRISPR screening, we identify molecular factors that restrict heritable memory of epialleles in naïve pluripotent cells, and demonstrate that removal of chromatin factor Dppa2 unlocks the potential for epigenetic inheritance uncoupled from DNA sequence. Our study outlines a mechanistic basis for how epigenetic inheritance is constrained in mammals, and reveals genomic and developmental contexts in which heritable memory is feasible.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.