ArticleNucleic acids research2019
Mutations of R882 change flanking sequence preferences of the DNA methyltransferase DNMT3A and cellular methylation patterns.
Article in Nucleic acids research, 2019. 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, 72 citations in OpenAlex.
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- Clonal hematopoiesis-associated DNMT3A mutations derepress bivalent Polycomb target genes and enhance macrophage migration.bioRxiv : the preprint server for biology · 2026Article
- 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
- TET CpG sequence-context-specific DNA demethylation shapes progression of IDH-mutant gliomas.Cell reports. Medicine · 2026Article
- Clonal Hematopoiesis and Incident Heart Failure.JAMA cardiology · 2026Article
- circKCNQ5 promotes the proliferation of DNA-methyltransferase 3A R882 mutated acute myeloid leukemia cells by elevating high-mobility group box 1 expression.Annals of medicine · 2025Article
- CD44v6 CAR-T Cells Target DNMT3A-Mutant AML: Synergistic Enhancement by Decitabine.Current medical science · 2025Article
- So close yet so far apart: distinct flanking sequence recognition by DNMT3A and DNMT3B.Communications biology · 2025Article
- Systematic analysis of specificities and flanking sequence preferences of bacterial DNA-(cytosine C5)-methyltransferases reveals mechanisms of enzyme- and sequence-specific DNA readout.Nucleic acids research · 2025Article
- DNMT3A-R882: a mutation with many paradoxes.Annals of hematology · 2024Review
- Molecular mechanisms for DNA methylation defects induced by ICF syndrome-linked mutations in DNMT3B.Protein science : a publication of the Protein Society · 2024Article
- Specific DNMT3C flanking sequence preferences facilitate methylation of young murine retrotransposons.Communications biology · 2024Article
- Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.Nature communications · 2024Article
- Structural basis for the allosteric regulation and dynamic assembly of DNMT3B.Nucleic acids research · 2023Article
- Identification of Cell Type-Specific Effects ofMolecules and cells · 2023Article
- Review
- Clonal hematopoiesis, somatic mosaicism, and age-associated disease.Physiological reviews · 2023Review
- Identification of three novel DNMT3A mutations with compromising methylation capacity in human acute myeloid leukaemia.Molecular biology reports · 2022Article
- Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.Nature genetics · 2022Article
- Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic DNMT3A mutations at R882 are frequently observed in AML patients including the very abundant R882H, but also R882C, R882P and R882S. Using deep enzymology, we show here that DNMT3A-R882H has more than 70-fold altered flanking sequence preferences when compared with wildtype DNMT3A. The R882H flanking sequence preferences mainly differ on the 3' side of the CpG site, where they resemble DNMT3B, while 5' flanking sequence preferences resemble wildtype DNMT3A, indicating that R882H behaves like a DNMT3A/DNMT3B chimera. Investigation of the activity and flanking sequence preferences of other mutations of R882 revealed that they cause similar effects. Bioinformatic analyses of genomic methylation patterns focusing on flanking sequence effects after expression of wildtype DNMT3A and R882H in human cells revealed that genomic methylation patterns reflect the details of the altered flanking sequence preferences of R882H. Concordantly, R882H specific hypermethylation in AML patients was strongly correlated with the R882H flanking sequence preferences. R882H specific DNA hypermethylation events in AML patients were accompanied by R882H specific mis-regulation of several genes with strong cancer connection, which are potential downstream targets of R882H. In conclusion, our data provide novel and detailed mechanistic understanding of the pathogenic mechanism of the DNMT3A R882H somatic cancer mutation.
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