ArticleNature structural & molecular biology2020
Dppa2 and Dppa4 counteract de novo methylation to establish a permissive epigenome for development.
Article in Nature structural & molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
- Embryonic stem cell factors DPPA2/4 amplify active H3K4me3-H2AK119ub chromatin domains in non-small cell lung cancer.Genes & development · 2026Article
- Chromatin profiling identifies putative dual roles for H3K27me3 in regulating cell type-specific genes and transposable elements in choanoflagellates.Nature communications · 2025Article
- Divergent roles of DNA methylation, TRIM28, and p53 surveillance in human embryonic and trophoblast stem cells.bioRxiv : the preprint server for biology · 2025Article
- Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis.Nature cell biology · 2025Article
- Expression of LINE-1 elements is required for preimplantation development and totipotency.Genes & diseases · 2025Review
- Ints7 deficiency activates DNA damage response to elicit resurgence of endogenous retrovirus MERVL and anastasis of embryonic stem cells.Nucleic acids research · 2025Article
- Histone bivalency in CNS development.Genes & development · 2025Review
- Functional genomic profiling of O-GlcNAc reveals its context-specific interplay with RNA polymerase II.Genome biology · 2025Article
- Saponins enhance the stability and cost-efficiency of human embryonic stem cell culture.Cell regeneration (London, England) · 2025Article
- TASOR expression in naive embryonic stem cells safeguards their developmental potential.Cell reports · 2024Article
- Expression Proteomics and Histone Analysis Reveal Extensive Chromatin Network Changes and a Role for Histone Tail Trimming during Cellular Differentiation.Biomolecules · 2024Article
- Bivalent chromatin: a developmental balancing act tipped in cancer.Biochemical Society transactions · 2024Review
- Article
- A low-input high resolution sequential chromatin immunoprecipitation method captures genome-wide dynamics of bivalent chromatin.Epigenetics & chromatin · 2024Article
- DNA methylation restricts coordinated germline and neural fates in embryonic stem cell differentiation.Nature structural & molecular biology · 2024Article
- A genome-wide screen reveals new regulators of the 2-cell-like cell state.Nature structural & molecular biology · 2023Article
- Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation.Nucleic acids research · 2023Article
- Esrrb guides naive pluripotent cells through the formative transcriptional programme.Nature cell biology · 2023Article
- Systematic identification of factors involved in the silencing of germline genes in mouse embryonic stem cells.Nucleic acids research · 2023Article
- Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components.Nucleic acids research · 2023Article
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early mammalian development entails genome-wide epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate DNA methylation dynamics, we coupled a single-cell ratiometric DNA methylation reporter with unbiased CRISPR screening in murine embryonic stem cells (ESCs). We identify key genes and regulatory pathways that drive global DNA hypomethylation, and characterize roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states. In their absence, developmental genes and evolutionarily young LINE1 elements, which are specifically bound by DPPA2, lose H3K4me3 and gain ectopic de novo DNA methylation in pluripotent cells. Consequently, lineage-associated genes and LINE1 acquire a repressive epigenetic memory, which renders them incompetent for activation during future lineage specification. Dppa2/4 thereby sculpt the pluripotent epigenome by facilitating H3K4me3 and bivalency to counteract de novo methylation, a function co-opted by evolutionarily young LINE1 to evade epigenetic decommissioning.
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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.