ArticleNature2018
Structural basis for DNMT3A-mediated de novo DNA methylation.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
204 citing papers in PubMed, 377 citations in OpenAlex.
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- 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
- Recent Advances in Searching for DNMT Inhibitors and Their Potential Application in Treating Human Diseases.International journal of molecular sciences · 2026Review
- Macrophage polarization-related genes with potential causal roles in osteoporosis: a multi-omics Mendelian randomization study.Journal of orthopaedic surgery and research · 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
- DNA Methylation Dynamics in Development and Disease: Insights from Zebrafish Models.Biomedicines · 2026Review
- Multi-omics clustering combined with multiple machine learning to identify epigenetic features in low-grade glioma patients.Translational cancer research · 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 signatures and causal factors underlying latent cytomegalovirus infection among people living with HIV (PLHIV).Nature communications · 2026Article
- Molecular basis for the inhibition of de novo DNA methylation by TCL1A.Nature communications · 2026Article
- Uncovering the acetylation sites of Dnmt3L that regulate protein stability and differentiation potency in embryonic stem cells.Experimental & molecular medicine · 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
- DNMT3A p.R882C driven proliferation and anti-apoptotic effects in pancreatic cancer cells.Scientific reports · 2026Article
- Mono-ubiquitination of histone H2A lysine 119 (H2AK119Ub): its multifaceted role in biology and implication in diseases.MedScience · 2026Review
- DNMT3A-mediated Methylation of IRF4 Alleviates Inflammatory Response in Allergic Rhinitis Mice.Applied biochemistry and biotechnology · 2026Article
- Comparative analysis of DNA methyltransferase 3 alpha and miR-29b expression in eutopic and ectopic endometrial tissues from endometriosis patients compared to healthy controls: A case-control study.International journal of reproductive biomedicine · 2026Article
- Mechanisms of DNMT3A-3L-mediated de novo DNA methylation on chromatin.Nature structural & molecular biology · 2026Article
- Versatile molecular tools enabling customizable DNA methylation editing in Arabidopsis.Nature communications · 2025Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
DNA methylation by de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) at cytosines is essential for genome regulation and development. Dysregulation of this process is implicated in various diseases, notably cancer. However, the mechanisms underlying DNMT3 substrate recognition and enzymatic specificity remain elusive. Here we report a 2.65-ångström crystal structure of the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides, with the target sites separated by 14 base pairs within the same DNA duplex. The DNMT3A-DNA interaction involves a target recognition domain, a catalytic loop, and DNMT3A homodimeric interface. Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. Haematological cancer-associated somatic mutations of the substrate-binding residues decrease DNMT3A activity, induce CpG hypomethylation, and promote transformation of haematopoietic cells. Together, our study reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its aetiological link to human disease.
Indexed as
Identifiers
What OpenQuestion holds
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.