ArticleMolecular and cellular biology2007
Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 245 citations in OpenAlex.
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Sendai virus-based human transcriptional gene delivery system fails to reprogram bovine mesenchymal stromal cells (MSC) into induced pluripotent stem cells (iPSC).Molecular biology reports · 2026Article
- Phylo-Epigenetic Conservation and CpG Erosion inGenes · 2025Article
- Article
- The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.Biomolecules · 2024Review
- DNMT3B PWWP mutations cause hypermethylation of heterochromatin.EMBO reports · 2024Article
- TET enzyme driven epigenetic reprogramming in early embryos and its implication on long-term health.Frontiers in cell and developmental biology · 2024Review
- Expression analysis suggests that DNMT3L is required for oocyte de novo DNA methylation only in Muridae and Cricetidae rodents.Epigenetics & chromatin · 2023Article
- Characterization of a Distinct State in the Continuum of Pluripotency Facilitated by Inhibition of PKCζ in Mouse Embryonic Stem Cells.Stem cell reviews and reports · 2023Article
- PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1.International journal of molecular sciences · 2023Article
- Review
- Regulation of Oct4 in stem cells and neural crest cells.Birth defects research · 2022Review
- Initiation of wound healing is regulated by the convergence of mechanical and epigenetic cues.PLoS biology · 2022Article
- Mitochondrial genome undergoes de novo DNA methylation that protects mtDNA against oxidative damage during the peri-implantation window.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- DNA methylation-independent long-term epigenetic silencing with dCRISPR/Cas9 fusion proteins.Life science alliance · 2022Article
- Physoxia Influences Global and Gene-Specific Methylation in Pluripotent Stem Cells.International journal of molecular sciences · 2022Article
- The disordered N-terminal domain of DNMT3A recognizes H2AK119ub and is required for postnatal development.Nature genetics · 2022Article
- Human embryonic mesenchymal lung-conditioned medium promotes differentiation to myofibroblast and loss of stemness phenotype in lung adenocarcinoma cell lines.Journal of experimental & clinical cancer research : CR · 2022Article
- Enzymology of Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- Domain Structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation plays an important role in gene silencing in mammals. Two de novo methyltransferases, Dnmt3a and Dnmt3b, are required for the establishment of genomic methylation patterns in development. However, little is known about their coordinate function in the silencing of genes critical for embryonic development and how their activity is regulated. Here we show that Dnmt3a and Dnmt3b are the major components of a native complex purified from embryonic stem cells. The two enzymes directly interact and mutually stimulate each other both in vitro and in vivo. The stimulatory effect is independent of the catalytic activity of the enzyme. In differentiating embryonic carcinoma or embryonic stem cells and mouse postimplantation embryos, they function synergistically to methylate the promoters of the Oct4 and Nanog genes. Inadequate methylation caused by ablating Dnmt3a and Dnmt3b is associated with dysregulated expression of Oct4 and Nanog during the differentiation of pluripotent cells and mouse embryonic development. These results suggest that Dnmt3a and Dnmt3b form a complex through direct contact in living cells and cooperate in the methylation of the promoters of Oct4 and Nanog during cell differentiation. The physical and functional interaction between Dnmt3a and Dnmt3b represents a novel regulatory mechanism to ensure the proper establishment of genomic methylation patterns for gene silencing in development.
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