ArticleNature communications2021
Structural basis of the regulation of the normal and oncogenic methylation of nucleosomal histone H3 Lys36 by NSD2.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- NSD Histone Methyltransferases in Solid Tumors: Biological Functions, Oncogenic Mechanisms and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Decoding the Conformational Dynamics and Hyperactivity of Histone H3K36 N-Methyltransferase in Oncogenic MutationsbioRxiv : the preprint server for biology · 2026Article
- Protein-Protein Cross-Linking by a DNA Damage-Derived Histone Modification.Journal of the American Chemical Society · 2026Article
- NSD2 inhibits the expression of PD-L1 via oxidative phosphorylation to control immune surveillance in hepatocellular carcinoma.Cell death & disease · 2026Article
- Article
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Identification of potential methyltransferase NSD2 enzymatic inhibitors through a multi-step structure-based drug design.Molecular diversity · 2025Article
- Research status of small molecule inhibitors, probes, and degraders of NSDs: a comprehensive review.Future medicinal chemistry · 2025Review
- Structural mechanism of H3K27 demethylation and crosstalk with heterochromatin markers.Molecular cell · 2025Article
- The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma.Nucleic acids research · 2025Article
- Recruitment of FBXO22 for targeted degradation of NSD2.Nature chemical biology · 2024Article
- Discovery of NSD2 non-histone substrates and design of a super-substrate.Communications biology · 2024Article
- NSD family proteins: Rising stars as therapeutic targets.Cell insight · 2024Review
- Structure of the human Bre1 complex bound to the nucleosome.Nature communications · 2024Article
- Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.Genes & development · 2024Article
- Structural insights into the C-terminus of the histone-lysine N-methyltransferase NSD3 by small-angle X-ray scattering.Frontiers in molecular biosciences · 2024Article
- Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2023Article
- Drug Discovery Targeting Nuclear Receptor Binding SET Domain Protein 2 (NSD2).Journal of medicinal chemistry · 2023Review
- Histone Maps inInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dimethylated histone H3 Lys36 (H3K36me2) regulates gene expression, and aberrant H3K36me2 upregulation, resulting from either the overexpression or point mutation of the dimethyltransferase NSD2, is found in various cancers. Here we report the cryo-electron microscopy structure of NSD2 bound to the nucleosome. Nucleosomal DNA is partially unwrapped, facilitating NSD2 access to H3K36. NSD2 interacts with DNA and H2A along with H3. The NSD2 autoinhibitory loop changes its conformation upon nucleosome binding to accommodate H3 in its substrate-binding cleft. Kinetic analysis revealed that two oncogenic mutations, E1099K and T1150A, increase NSD2 catalytic turnover. Molecular dynamics simulations suggested that in both mutants, the autoinhibitory loop adopts an open state that can accommodate H3 more often than the wild-type. We propose that E1099K and T1150A destabilize the interactions that keep the autoinhibitory loop closed, thereby enhancing catalytic turnover. Our analyses guide the development of specific inhibitors of NSD2.
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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.