ArticleThe Journal of biological chemistry2016
A PWWP Domain of Histone-Lysine N-Methyltransferase NSD2 Binds to Dimethylated Lys-36 of Histone H3 and Regulates NSD2 Function at Chromatin.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 108 citations in OpenAlex.
- Spatial partitioning of NSD2 defines H3K36me2 as an active mark for repetitive sequence activation.Nature communications · 2026Article
- Deep phenotyping of EHMT1 ankyrin repeat domain missense variants in Kleefstra syndrome by multi-tiered structural genomics analyses at atomic resolution.Human molecular genetics · 2026Article
- Decoding the Conformational Dynamics and Hyperactivity of Histone H3K36 N-Methyltransferase in Oncogenic MutationsbioRxiv : the preprint server for biology · 2026Article
- Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22.Nature communications · 2026Article
- Many faces of mammalian NSD methyltransferases.Cellular & molecular biology letters · 2026Review
- Structural Genomics Defines PBRM1 Bromodomain Variant Function in ccRCC.Human mutation · 2026Article
- NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities.Biomedicines · 2025Review
- Nucleosome context regulates chromatin reader preference.Nucleic acids research · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1.Cell reports · 2025Article
- Structural and Molecular Insight into the PWWP1 Domain of NSD2 from the Discovery of Novel Binders Via DNA-Encoded Library Screening.ACS medicinal chemistry letters · 2025Article
- Research status of small molecule inhibitors, probes, and degraders of NSDs: a comprehensive review.Future medicinal chemistry · 2025Review
- The epigenetic circle: feedback loops in the maintenance of cellular memory.Epigenetics & chromatin · 2025Review
- Mutation of a gene with PWWP domain confers salt tolerance in rice.Plant molecular biology · 2025Article
- The sotos syndrome gene Nsd1 safeguards developmental gene enhancers poised for transcription by maintaining the precise deposition of histone methylation.The Journal of biological chemistry · 2025Article
- Integrated Network Pharmacology, Molecular Modeling, LC-MS Profiling, and Semisynthetic Approach for the Roots ofACS omega · 2025Article
- Structural basis of thymidine-rich DNA recognition by Drosophila P75 PWWP domain.Communications biology · 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
- Using human disease mutations to understand de novo DNA methyltransferase function.Biochemical Society transactions · 2024Review
- Intestinal NSD2 Aggravates Nonalcoholic Steatohepatitis Through Histone Modifications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The readout of histone modifications plays a critical role in chromatin-regulated processes. Dimethylation at Lys-36 on histone H3 (H3K36me2) is associated with actively transcribed genes, and global up-regulation of this modification is associated with several cancers. However, the molecular mechanism by which H3K36me2 is sensed and transduced to downstream biological outcomes remains unclear. Here we identify a PWWP domain within the histone lysine methyltransferase and oncoprotein NSD2 that preferentially binds to nucleosomes containing H3K36me2. In cells, the NSD2 PWWP domain interaction with H3K36me2 plays a role in stabilizing NSD2 at chromatin. Furthermore, NSD2's ability to induce global increases in H3K36me2 via its enzymatic activity, and consequently promote cellular proliferation, is compromised by mutations within the PWWP domain that specifically abrogate H3K36me2-recognition. Together, our results identify a pivotal role for NSD2 binding to its catalytic product in regulating its cellular functions, and suggest a model for how this interaction may facilitate epigenetic spreading and propagation of H3K36me2.
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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.