ArticleNature communications2020
Structural basis for impairment of DNA methylation by the DNMT3A R882H mutation.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 77 citations in OpenAlex.
- 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
- Protein loops are major contributors to DNA strand separation and high-fidelity substrate recognition for DNA methyltransferase CcrM.The Journal of biological chemistry · 2026Article
- DNMT3A in cancer: from epigenetic writer to oncogenic driver.Clinical epigenetics · 2026Review
- Mutation-specific impairment of TET2 and DNMT3A enzymatic activity predicts clonal hematopoiesis disease risk.medRxiv : the preprint server for health sciences · 2026Article
- Molecular basis for the inhibition of de novo DNA methylation by TCL1A.Nature communications · 2026Article
- DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency.Cancer discovery · 2026Article
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- Structural insight into hierarchical DNMT3A autoinhibition and its dysregulation in disease.Nature communications · 2026Article
- Comprehensive profiling of CRISPR/dCas9 epigenome editors indicates a complex link between on and off target effects.Genome biology · 2026Article
- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.Military Medical Research · 2025Review
- Structure of an Unfavorable de Novo DNA Methylation Complex of Plant Methyltransferase ZMET2.Journal of molecular biology · 2025Article
- So close yet so far apart: distinct flanking sequence recognition by DNMT3A and DNMT3B.Communications biology · 2025Article
- Polyamines at the crossroad between cell metabolism and epigenetic regulation in acute leukemias.Cell death discovery · 2025Review
- The role of global DNA methylation in citrinin induced toxicity:Toxicology reports · 2025Article
- Endocrine-disrupting chemicals (EDCs) and epigenetic regulation in embryonic development: Mechanisms, impacts, and emerging trends.Toxicology reports · 2025Review
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- DNMT3A-R882: a mutation with many paradoxes.Annals of hematology · 2024Review
- Can dental problems be indicative of clonal hematopoiesis?Cell research · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
DNA methyltransferase DNMT3A is essential for establishment of mammalian DNA methylation during development. The R882H DNMT3A is a hotspot mutation in acute myeloid leukemia (AML) causing aberrant DNA methylation. However, how this mutation affects the structure and function of DNMT3A remains unclear. Here we report structural characterization of wild-type and R882H-mutated DNMT3A in complex with DNA substrates with different sequence contexts. A loop from the target recognition domain (TRD loop) recognizes the CpG dinucleotides in a +1 flanking site-dependent manner. The R882H mutation reduces the DNA binding at the homodimeric interface, as well as the molecular link between the homodimeric interface and TRD loop, leading to enhanced dynamics of TRD loop. Consistently, in vitro methylation analyses indicate that the R882H mutation compromises the enzymatic activity, CpG specificity and flanking sequence preference of DNMT3A. Together, this study uncovers multiple defects of DNMT3A caused by the R882H mutation in AML.
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Registered trials
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.