ArticleNature2014
The DNA methylation landscape of human early embryos.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 508 papers, 1 of them a synthesis that pooled it.
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
508 citing papers in PubMed, 1 synthesis or guideline pooled it, 921 citations in OpenAlex.
- A systematic review of neuroimaging epigenetic research: calling for an increased focus on development.Molecular psychiatry · 2023Pooled it
- Altered sperm DNA methylation provides an epigenetic route from overweight and older men to intergenerational disease transmission.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Establishing Polycomb regulatory landscapes in human early development.Nature genetics · 2026Article
- Sperm AluY Epimutations in Male Partners of Couples with Unexplained Recurrent Pregnancy Loss.bioRxiv : the preprint server for biology · 2026Article
- Single-cell transcriptomic analysis reveals subtle fluctuations of oocyte cryopreservation on mouse early embryo development.Clinical and translational medicine · 2026Article
- Multi-omics and developmental comparison of direct and conventional warming methods in vitrified human and mouse cleavage-stage embryos.Human reproduction (Oxford, England) · 2026Article
- The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026Review
- NICE: A Two-Step Non-Invasive Framework for Embryo cfDNA Read Enrichment and Quality Assessment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The length of the embryo culture in assisted reproductive technology does not have a major impact on newborn DNA methylation.Bioscience reports · 2026Article
- Landscape of parental postzygotic mutations across >11,000 rare disease trios.American journal of human genetics · 2026Article
- Embracing non-linearity in human ageing.Nature reviews. Genetics · 2026Review
- 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
- Dissecting the expression pattern during embryonic development and unveiling sustained ZGA genes with oncogenic relevance.BMC genomics · 2026Article
- Population epigenetics: deciphering DNA methylation diversity and its implications for health, disease, and evolution.Molecular biology and evolution · 2026Review
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Sex-specific associations between psychological resilience and blastocyst quality.Reproduction & fertility · 2026Observational
- DNA methylation reprogramming in marsupial embryos is restricted to the extraembryonic lineage.Nature communications · 2026Article
- MECP2 mutations rewire human ESC fate and bias cortical lineage commitment.Stem cell reports · 2026Article
- The dynamic expression pattern of signaling pathways involved in early embryo development.Cell communication and signaling : CCS · 2026Article
- From germline immortality to somatic rejuvenation: Unlocking the ovarian blueprint for longevity.PLoS biology · 2026Article
448 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development. However, its dynamic patterns have not been analysed at the genome scale in human pre-implantation embryos due to technical difficulties and the scarcity of required materials. Here we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by reduced representation bisulphite sequencing and whole-genome bisulphite sequencing. We show that the major wave of genome-wide demethylation is complete at the 2-cell stage, contrary to previous observations in mice. Moreover, the demethylation of the paternal genome is much faster than that of the maternal genome, and by the end of the zygotic stage the genome-wide methylation level in male pronuclei is already lower than that in female pronuclei. The inverse correlation between promoter methylation and gene expression gradually strengthens during early embryonic development, reaching its peak at the post-implantation stage. Furthermore, we show that active genes, with the trimethylation of histone H3 at lysine 4 (H3K4me3) mark at the promoter regions in pluripotent human embryonic stem cells, are essentially devoid of DNA methylation in both mature gametes and throughout pre-implantation development. Finally, we also show that long interspersed nuclear elements or short interspersed nuclear elements that are evolutionarily young are demethylated to a milder extent compared to older elements in the same family and have higher abundance of transcripts, indicating that early embryos tend to retain higher residual methylation at the evolutionarily younger and more active transposable elements. Our work provides insights into the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements.
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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.