ArticleCell discovery2021
Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations.
Article in Cell discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Regulation of the histone H3K36 methyltransferase Set2 by the histone chaperone Spt6.Nucleic acids research · 2026Article
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- Regulation of the histone H3K36 methyltransferase Set2 by the histone chaperone Spt6.bioRxiv : the preprint server for biology · 2026Article
- CLOCK-catalyzed histone H3K37 glutarylation suppresses H3K36 trimethylation pathways in glioblastoma.Science advances · 2026Article
- Article
- The SETD2 L1609P mutation found in leukemia disrupts methyltransferase activity and reduces histone H3K36 trimethylation.The Journal of biological chemistry · 2026Article
- Assembling Ternary Dead-End Complex for Covalent Trapping of Protein Lysine Methyltransferases.Journal of the American Chemical Society · 2026Article
- Structural basis of transcription-coupled H3K36 trimethylation by Set2 in coordination with FACT.Science advances · 2026Article
- MYC drives left-handed Z-DNA formation to shape gene expression.Nature communications · 2025Article
- Molecular mechanism of co-transcriptional H3K36 methylation by SETD2.Nature communications · 2025Article
- SETD2 suppresses tumorigenesis in a KRASeLife · 2025Article
- Structural mechanism of H3K27 demethylation and crosstalk with heterochromatin markers.Molecular cell · 2025Article
- Nanoscale analysis of human G1 and metaphase chromatin in situ.The EMBO journal · 2025Article
- Beyond the mono-nucleosome.Biochemical Society transactions · 2025Review
- Structural basis of H3K36 trimethylation by SETD2 during chromatin transcription.Science (New York, N.Y.) · 2025Article
- Catalytic activity of Setd2 is essential for embryonic development in mice: establishment of a mouse model harboring patient-derived Setd2 mutation.Frontiers of medicine · 2024Article
- Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model.Journal of fungi (Basel, Switzerland) · 2023Review
- The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications.Protein & cell · 2023Review
- Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma.Frontiers in oncology · 2023Review
- Clinical and genetic features of luscan-lumish syndrome associated with a novel de novo variant ofFrontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. To investigate how the oncohistone mutation affects the function of SETD2 at the nucleosome level, we determined the cryo-EM structure of human SETD2 associated with an H3.3K36M nucleosome and cofactor S-adenosylmethionine (SAM), and revealed that SETD2 is attached to the N-terminal region of histone H3 and the nucleosome DNA at superhelix location 1, accompanied with the partial unwrapping of nucleosome DNA to expose the SETD2-binding site. These structural features were also observed in the previous cryo-EM structure of the fungal Set2-nucleosome complex. By contrast with the stable association of SETD2 with the H3.3K36M nucleosome, the EM densities of SETD2 could not be observed on the wild-type nucleosome surface, suggesting that the association of SETD2 with wild-type nucleosome might be transient. The linker histone H1, which stabilizes the wrapping of nucleosome DNA at the entry/exit sites, exhibits an inhibitory effect on the activities of SETD2 and displays inversely correlated genome distributions with that of the H3K36me3 marks. Cryo-EM analysis of yeast H3K36 methyltransferase Set2 complexed with nucleosomes further revealed evolutionarily conserved structural features for nucleosome recognition in eukaryotes, and provides insights into the mechanism of activity regulation. These findings have advanced our understanding of the structural basis for the tumorigenesis mechanism of the H3.3K36M mutation and highlight the effect of nucleosome conformation on the regulation of histone modification.
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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.