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Yorodumi- PDB-8vnz: PRC2_AJ1-450 bound to H3K36me3-modified nucleosome with histone H... -
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Open data
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Basic information
| Entry | Database: PDB / ID: 8vnz | |||||||||||||||||||||||||||||||||
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| Title | PRC2_AJ1-450 bound to H3K36me3-modified nucleosome with histone H3 tail disengaged | |||||||||||||||||||||||||||||||||
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Keywords | GENE REGULATION / complex / methyltransferase / histone / epigenetics | |||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationhepatocyte homeostasis / regulation of kidney development / cellular response to trichostatin A / negative regulation of striated muscle cell differentiation / regulation of gliogenesis / negative regulation of keratinocyte differentiation / random inactivation of X chromosome / [histone H3]-lysine27 N-trimethyltransferase / response to tetrachloromethane / CAF-1 complex ...hepatocyte homeostasis / regulation of kidney development / cellular response to trichostatin A / negative regulation of striated muscle cell differentiation / regulation of gliogenesis / negative regulation of keratinocyte differentiation / random inactivation of X chromosome / [histone H3]-lysine27 N-trimethyltransferase / response to tetrachloromethane / CAF-1 complex / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / negative regulation of retinoic acid receptor signaling pathway / histone H3K27 trimethyltransferase activity / cerebellar cortex development / primary miRNA binding / histone H3K27 methyltransferase activity / ubiquitin-modified histone reader activity / sex chromatin / positive regulation of cell cycle G1/S phase transition / NURF complex / regulatory ncRNA-mediated heterochromatin formation / cardiac muscle hypertrophy in response to stress / negative regulation of stem cell differentiation / facultative heterochromatin formation / NuRD complex / regulation of cell fate specification / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / regulation of stem cell differentiation / ESC/E(Z) complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / RSC-type complex / protein-lysine N-methyltransferase activity / oligodendrocyte differentiation / Polo-like kinase mediated events / chromatin silencing complex / Transcription of E2F targets under negative control by DREAM complex / pronucleus / positive regulation of dendrite development / histone H3K9me2/3 reader activity / DNA methylation-dependent constitutive heterochromatin formation / histone H3 methyltransferase activity / negative regulation of G1/S transition of mitotic cell cycle / G1 to G0 transition / synaptic transmission, GABAergic / histone methyltransferase activity / Sin3-type complex / negative regulation of gene expression, epigenetic / G1/S-Specific Transcription / spinal cord development / positive regulation of stem cell population maintenance / positive regulation of MAP kinase activity / lncRNA binding / histone deacetylase complex / negative regulation of transcription elongation by RNA polymerase II / positive regulation of protein serine/threonine kinase activity / histone methyltransferase complex / Transcriptional Regulation by E2F6 / RNA Polymerase I Transcription Initiation / G0 and Early G1 / keratinocyte differentiation / subtelomeric heterochromatin formation / positive regulation of GTPase activity / negative regulation of cell differentiation / ribonucleoprotein complex binding / positive regulation of epithelial to mesenchymal transition / Cyclin E associated events during G1/S transition / RNA polymerase II core promoter sequence-specific DNA binding / pericentric heterochromatin / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / Cyclin A:Cdk2-associated events at S phase entry / Regulation of TP53 Activity through Acetylation / nucleosome binding / heterochromatin / B cell differentiation / protein localization to chromatin / negative regulation of cytokine production involved in inflammatory response / liver regeneration / Deposition of new CENPA-containing nucleosomes at the centromere / negative regulation of cell migration / stem cell differentiation / hippocampus development / transcription corepressor binding / SUMOylation of chromatin organization proteins / Regulation of PTEN gene transcription / central nervous system development / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / brain development / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / ubiquitin binding / transcription coregulator activity / HDACs deacetylate histones / G1/S transition of mitotic cell cycle / negative regulation of transforming growth factor beta receptor signaling pathway / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / promoter-specific chromatin binding / cell population proliferation / chromatin DNA binding Similarity search - Function | |||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | |||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||||||||||||||||||||||||||
Authors | Cookis, T. / Nogales, E. | |||||||||||||||||||||||||||||||||
| Funding support | United States, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2025Title: Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications. Authors: Trinity Cookis / Alexandria Lydecker / Paul Sauer / Vignesh Kasinath / Eva Nogales / ![]() Abstract: Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is ...Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms. Using cryo-electron microscopy, we reveal that histone H3 tails containing H3K36me3 engage poorly with PRC2 and preclude its effective interaction with chromatin, while H3K4me3 binds to the allosteric site in the EED subunit, acting as an antagonist that competes with activators required for spreading of the H3K27me3 repressive mark. Thus, the location of the H3K4me3 and H3K36me3 modifications along the H3 tail allows them to target two requirements for efficient trimethylation of H3K27 by PRC2. We further show that the JARID2 cofactor modulates PRC2 activity in the presence of these histone modifications. | |||||||||||||||||||||||||||||||||
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 8vnz.cif.gz | 387.7 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb8vnz.ent.gz | 289.4 KB | Display | PDB format |
| PDBx/mmJSON format | 8vnz.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vn/8vnz ftp://data.pdbj.org/pub/pdb/validation_reports/vn/8vnz | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 43362MC ![]() 8vmiC ![]() 8vmjC ![]() 8vmlC ![]() 8vmnC ![]() 8vnvC ![]() 8vo0C ![]() 8vobC M: map data used to model this data C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
-Polycomb protein ... , 2 types, 2 molecules AL
| #1: Protein | Mass: 83181.922 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SUZ12, CHET9, JJAZ1, KIAA0160 / Cell line (production host): Sf9 / Production host: ![]() |
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| #2: Protein | Mass: 50267.691 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EED / Cell line (production host): Sf9 / Production host: ![]() |
-Protein , 4 types, 4 molecules NCBP
| #3: Protein | Mass: 47709.527 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RBBP4, RBAP48 / Cell line (production host): Sf9 / Production host: ![]() |
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| #4: Protein | Mass: 85492.297 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EZH2, KMT6 / Cell line (production host): Sf9 / Production host: ![]() References: UniProt: Q15910, [histone H3]-lysine27 N-trimethyltransferase |
| #5: Protein | Mass: 49174.879 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: JARID2, JMJ / Production host: ![]() |
| #6: Protein | Mass: 34042.133 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AEBP2 / Cell line (production host): Sf9 / Production host: ![]() |
-Non-polymers , 1 types, 1 molecules 
| #7: Chemical | ChemComp-SAH / |
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-Details
| Has ligand of interest | N |
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| Has protein modification | Y |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: PRC2_AJ1-450 bound to H3K36me3-modified nucleosome / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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| Molecular weight | Value: 0.35 MDa / Experimental value: NO |
| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: ![]() |
| Buffer solution | pH: 7.5 |
| Specimen | Conc.: 0.28 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 291 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 44519 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi



Homo sapiens (human)
United States, 2items
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FIELD EMISSION GUN