ArticleNature2017
Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
120 citing papers in PubMed.
- Multiplexed single-cell reduced representation bisulfite sequencing for genome-wide DNA methylation profiling.Nature protocols · 2026Review
- Folate deficiency disrupts key metabolic transitions within the developing neural ectoderm.bioRxiv : the preprint server for biology · 2026Article
- Mammalian DNA methyltransferases in DNA methylation and imprinted gene expression in extraembryonic ectoderm of post-implantation embryos.The Journal of biological chemistry · 2026Article
- Embryo vitrification disturbs the pre-implantation DNA demethylation process and affects hepatic functions to threaten long-term metabolic health in mice.Journal of advanced research · 2026Article
- Epigenetic blind spots - the role of DNA methylation dynamics in stem cell-based models of embryogenesis.FEBS letters · 2026Article
- Conserved and divergent DNA methylation features of extraembryonic tissues between human, mouse and chicken.BMC genomics · 2026Article
- DNA methylation reprogramming in marsupial embryos is restricted to the extraembryonic lineage.Nature communications · 2026Article
- Review
- Fertilization with Protamine-2 deficient sperm triggers abnormal pronucleus development and zygotic cleavage†.Biology of reproduction · 2026Article
- Epigenetic Deregulation of Transposable Elements Links Developmental Processes and Tumorigenesis.International journal of molecular sciences · 2026Review
- Lamin A/C directs nucleosome-scale chromatin remodeling to define early lineage segregation in mammals.bioRxiv : the preprint server for biology · 2026Article
- Evolution of Cancer Metastases via Lineage Trans-Differentiation.Research (Washington, D.C.) · 2026Article
- Reprogramming of H3K36me2 guides lineage-specific post-implantation de novo DNA methylation.Nature cell biology · 2025Article
- Epigenetic control of cell identities from epiblast to gastrulation.The FEBS journal · 2025Review
- Direct genetic transformation bypasses tumor-associated DNA methylation alterations.Genome biology · 2025Article
- The rebirth of repressive chromatin during early vertebrate development.Annals of the New York Academy of Sciences · 2025Review
- Article
- Cell-context response to germ layer differentiation signals is predetermined by the epigenome in regionalized epiblast populations.Nature communications · 2025Article
- Sex-differentiated placental methylation and gene expression regulation has implications for neonatal traits and adult diseases.Nature communications · 2025Article
- From Lineage to Longevity: A Field Guide to the Key Players in Epigenetic Contribution to Offspring Health.Current issues in molecular biology · 2025Review
60 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
In mammals, the canonical somatic DNA methylation landscape is established upon specification of the embryo proper and subsequently disrupted within many cancer types. However, the underlying mechanisms that direct this genome-scale transformation remain elusive, with no clear model for its systematic acquisition or potential developmental utility. Here, we analysed global remethylation from the mouse preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions with substantial disruption of bimodal, CpG density-dependent methylation in the placental progenitor. The extraembryonic epigenome includes specific de novo methylation at hundreds of embryonically protected CpG island promoters, particularly those that are associated with key developmental regulators and are orthologously methylated across most human cancer types. Our data suggest that the evolutionary innovation of extraembryonic tissues may have required co-option of DNA methylation-based suppression as an alternative to regulation by Polycomb-group proteins, which coordinate embryonic germ-layer formation in response to extraembryonic cues. Moreover, we establish that this decision is made deterministically, downstream of promiscuously used-and frequently oncogenic-signalling pathways, via a novel combination of epigenetic cofactors. Methylation of developmental gene promoters during tumorigenesis may therefore reflect the misappropriation of an innate trajectory and the spontaneous reacquisition of a latent, developmentally encoded epigenetic landscape.
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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.