+Open data
-Basic information
Entry | Database: PDB / ID: 7at8 | |||||||||
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Title | Histone H3 recognition by nucleosome-bound PRC2 subunit EZH2. | |||||||||
Components |
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Keywords | GENE REGULATION / Polycomb / nucleosome / histone methyltransferase / PRC2 / EZH2 / H3K36 / H3 tail / H3 / histone H3 / Polycomb Repressive Complex 2 / cryo-EM / nucleosome recognition / H3K36me2 / H3K36me3 | |||||||||
Function / homology | Function and homology information negative regulation of epidermal cell differentiation / : / : / transcription corepressor binding => GO:0001222 / subtelomeric heterochromatin formation => GO:0031509 / : / : / : / regulation of kidney development / hepatocyte homeostasis ...negative regulation of epidermal cell differentiation / : / : / transcription corepressor binding => GO:0001222 / subtelomeric heterochromatin formation => GO:0031509 / : / : / : / regulation of kidney development / hepatocyte homeostasis / cellular response to trichostatin A / regulation of gliogenesis / [histone H3]-lysine27 N-trimethyltransferase / negative regulation of striated muscle cell differentiation / sex chromatin / negative regulation of keratinocyte differentiation / histone H3K27 trimethyltransferase activity / negative regulation of retinoic acid receptor signaling pathway / random inactivation of X chromosome / primary miRNA binding / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / response to tetrachloromethane / cerebellar cortex development / facultative heterochromatin formation / histone H3K27 methyltransferase activity / positive regulation of cell cycle G1/S phase transition / chromatin => GO:0000785 / negative regulation of G0 to G1 transition / chromatin silencing complex / ESC/E(Z) complex / protein-lysine N-methyltransferase activity / negative regulation of stem cell differentiation / RSC-type complex / pronucleus / cardiac muscle hypertrophy in response to stress / synaptic transmission, GABAergic / lncRNA binding / positive regulation of dendrite development / histone H3 methyltransferase activity / negative regulation of gene expression, epigenetic / G1 to G0 transition / negative regulation of G1/S transition of mitotic cell cycle / histone methyltransferase activity / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / negative regulation of transcription elongation by RNA polymerase II / negative regulation of cell differentiation / subtelomeric heterochromatin formation / negative regulation of cytokine production involved in inflammatory response / RNA polymerase II core promoter sequence-specific DNA binding / pericentric heterochromatin / ribonucleoprotein complex binding / heterochromatin formation / positive regulation of epithelial to mesenchymal transition / keratinocyte differentiation / enzyme activator activity / protein localization to chromatin / methylated histone binding / SUMOylation of chromatin organization proteins / B cell differentiation / transcription corepressor binding / positive regulation of GTPase activity / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / Defective pyroptosis / liver regeneration / stem cell differentiation / hippocampus development / promoter-specific chromatin binding / positive regulation of MAP kinase activity / protein modification process / positive regulation of protein serine/threonine kinase activity / regulation of circadian rhythm / negative regulation of DNA-binding transcription factor activity / chromatin DNA binding / PKMTs methylate histone lysines / cellular response to hydrogen peroxide / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / G1/S transition of mitotic cell cycle / structural constituent of chromatin / transcription corepressor activity / nucleosome / rhythmic process / nucleosome assembly / response to estradiol / chromatin organization / methylation / Oxidative Stress Induced Senescence / cell population proliferation / chromosome, telomeric region / nuclear body / ribonucleoprotein complex / protein heterodimerization activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / synapse / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) Xenopus laevis (African clawed frog) synthetic construct (others) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.4 Å | |||||||||
Authors | Finogenova, K. / Benda, C. / Schaefer, I.B. / Poepsel, S. / Strauss, M. / Mueller, J. | |||||||||
Funding support | Germany, 2items
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Citation | Journal: Elife / Year: 2020 Title: Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3. Authors: Ksenia Finogenova / Jacques Bonnet / Simon Poepsel / Ingmar B Schäfer / Katja Finkl / Katharina Schmid / Claudia Litz / Mike Strauss / Christian Benda / Jürg Müller / Abstract: Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 ...Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface. Mutation of H3K36 to arginine or alanine inhibits H3K27 methylation by PRC2 on nucleosomes . Accordingly, H3K36A and H3K36R mutants show reduced levels of H3K27me3 and defective Polycomb repression of HOX genes. The relay of interactions between EZH2, the nucleosomal DNA and the H3 N-terminus therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in transcriptionally active chromatin. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7at8.cif.gz | 400.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7at8.ent.gz | 295.1 KB | Display | PDB format |
PDBx/mmJSON format | 7at8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7at8_validation.pdf.gz | 835.4 KB | Display | wwPDB validaton report |
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Full document | 7at8_full_validation.pdf.gz | 855.9 KB | Display | |
Data in XML | 7at8_validation.xml.gz | 42.2 KB | Display | |
Data in CIF | 7at8_validation.cif.gz | 66.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/at/7at8 ftp://data.pdbj.org/pub/pdb/validation_reports/at/7at8 | HTTPS FTP |
-Related structure data
Related structure data | 11910MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 6 types, 10 molecules ACDHEIFJGK
#1: Protein | Mass: 87195.328 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: EZH2, KMT6 / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q15910-2, UniProt: Q15910*PLUS, [histone H3]-lysine27 N-trimethyltransferase | ||||||
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#2: 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 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: Q15022 | ||||||
#3: Protein | Mass: 15303.930 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P84233 #4: Protein | Mass: 11263.231 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P62799 #5: Protein | Mass: 13978.241 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Gene: hist1h2aj, LOC494591 / Production host: Escherichia coli (E. coli) / References: UniProt: Q6AZJ8, UniProt: P06897*PLUS #6: Protein | Mass: 13524.752 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Xenopus laevis (African clawed frog) / Production host: Escherichia coli (E. coli) / References: UniProt: P02281 |
-Widom601 DNA plus ... , 2 types, 2 molecules TU
#7: DNA chain | Mass: 47904.535 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
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#8: DNA chain | Mass: 48402.852 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Non-polymers , 2 types, 8 molecules
#9: Chemical | ChemComp-ZN / #10: Chemical | ChemComp-SAH / | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
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Source (recombinant) |
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Buffer solution | pH: 7.8 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE-PROPANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 52.96 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 4.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 45849 / Symmetry type: POINT |