ArticleNucleic acids research2020
The acute myeloid leukemia variant DNMT3A Arg882His is a DNMT3B-like enzyme.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Gene expression profiling and pathway analysis in acute myeloid leukaemia-normal karyotype patients.PloS one · 2025Article
- Using human disease mutations to understand de novo DNA methyltransferase function.Biochemical Society transactions · 2024Review
- Molecular mechanisms for DNA methylation defects induced by ICF syndrome-linked mutations in DNMT3B.Protein science : a publication of the Protein Society · 2024Article
- Structure-guided functional suppression of AML-associated DNMT3A hotspot mutations.Nature communications · 2024Article
- Structural basis for the allosteric regulation and dynamic assembly of DNMT3B.Nucleic acids research · 2023Article
- Dnmt3bas coordinates transcriptional induction and alternative exon inclusion to promote catalytically active Dnmt3b expression.Cell reports · 2023Article
- Mediating and maintaining methylation while minimizing mutation: Recent advances on mammalian DNA methyltransferases.Current opinion in structural biology · 2022Review
- Enzymology of Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- Genetic Studies on Mammalian DNA Methyltransferases.Advances in experimental medicine and biology · 2022Article
- The language of chromatin modification in human cancers.Nature reviews. Cancer · 2021Review
- DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A.Biomolecules · 2021Article
- Alterations toCancer research · 2021Review
- Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B.Nucleic acids research · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We have previously shown that the highly prevalent acute myeloid leukemia (AML) mutation, Arg882His, in DNMT3A disrupts its cooperative mechanism and leads to reduced enzymatic activity, thus explaining the genomic hypomethylation in AML cells. However, the underlying cause of the oncogenic effect of Arg882His in DNMT3A is not fully understood. Here, we discovered that DNMT3A WT enzyme under conditions that favor non-cooperative kinetic mechanism as well as DNMT3A Arg882His variant acquire CpG flanking sequence preference akin to that of DNMT3B, which is non-cooperative. We tested if DNMT3A Arg882His could preferably methylate DNMT3B-specific target sites in vivo. Rescue experiments in Dnmt3a/3b double knockout mouse embryonic stem cells show that the corresponding Arg878His mutation in mouse DNMT3A severely impairs its ability to methylate major satellite DNA, a DNMT3A-preferred target, but has no overt effect on the ability to methylate minor satellite DNA, a DNMT3B-preferred target. We also observed a previously unappreciated CpG flanking sequence bias in major and minor satellite repeats that is consistent with DNMT3A and DNMT3B specificity suggesting that DNA methylation patterns are guided by the sequence preference of these enzymes. We speculate that aberrant methylation of DNMT3B target sites could contribute to the oncogenic potential of DNMT3A AML variant.
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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.