ArticleNature communications2023
Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- TRIM37 interacts with TRIM28 to maintain primordial germ cell identity during migration.Cell research · 2026Article
- Epigenetic blind spots - the role of DNA methylation dynamics in stem cell-based models of embryogenesis.FEBS letters · 2026Article
- T cell senescence induced by DNMT1 deletion mediates cardiac transplant tolerance via altered CDKN1A methylation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Spatial 5mC-seq profiling of embryos and decidua after implantation in mammals.Nature methods · 2026Article
- Epigenetic mechanisms in maternal-fetal crosstalk: inter- and trans-generational inheritance.Epigenomics · 2025Review
- Correcting a patient-specific Rhodopsin mutation with adenine base editor in a mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- DNA methylation in mammalian development and disease.Nature reviews. Genetics · 2025Review
- Efficient prime editing in two-cell mouse embryos using PEmbryo.Nature biotechnology · 2024Article
- Deciphering DNA Methylation in Gestational Diabetes Mellitus: Epigenetic Regulation and Potential Clinical Applications.International journal of molecular sciences · 2024Review
- Antibody Fc-receptor FcεR1γ stabilizes cell surface receptors in group 3 innate lymphoid cells and promotes anti-infection immunity.Nature communications · 2024Article
- Single-Cell RNA Sequencing of Mutant Whole Mouse Embryos: From the Epiblast to the End of Gastrulation.Journal of visualized experiments : JoVE · 2024Article
- Systematic Characterization of DNA Methyltransferases Family in Tumor Progression and Antitumor Immunity.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During embryo development, DNA methylation is established by DNMT3A/3B and subsequently maintained by DNMT1. While much research has been done in this field, the functional significance of DNA methylation in embryogenesis remains unknown. Here, we establish a system of simultaneous inactivation of multiple endogenous genes in zygotes through screening for base editors that can efficiently introduce a stop codon. Embryos with mutations in Dnmts and/or Tets can be generated in one step with IMGZ. Dnmt-null embryos display gastrulation failure at E7.5. Interestingly, although DNA methylation is absent, gastrulation-related pathways are down-regulated in Dnmt-null embryos. Moreover, DNMT1, DNMT3A, and DNMT3B are critical for gastrulation, and their functions are independent of TET proteins. Hypermethylation can be sustained by either DNMT1 or DNMT3A/3B at some promoters, which are related to the suppression of miRNAs. The introduction of a single mutant allele of six miRNAs and paternal IG-DMR partially restores primitive streak elongation in Dnmt-null embryos. Thus, our results unveil an epigenetic correlation between promoter methylation and suppression of miRNA expression for gastrulation and demonstrate that IMGZ can accelerate deciphering the functions of multiple genes in vivo.
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