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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23024 | |||||||||
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Title | PRC2:EZH1_A from a dimeric PRC2 bound to a nucleosome | |||||||||
![]() | PRC2:EZH1_A from a dimeric PRC2 bound to a nucleosome | |||||||||
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![]() | Chromatin / methyltransferase / nucleosome-modifying complex / GENE REGULATION / GENE REGULATION-Transferase complex | |||||||||
Function / homology | ![]() [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / facultative heterochromatin formation / histone H3K27 methyltransferase activity / NURF complex / regulation of cell fate specification / negative regulation of stem cell population maintenance ...[histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / facultative heterochromatin formation / histone H3K27 methyltransferase activity / NURF complex / regulation of cell fate specification / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / NuRD complex / chromatin silencing complex / ESC/E(Z) complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / RSC-type complex / Transcription of E2F targets under negative control by DREAM complex / Polo-like kinase mediated events / lncRNA binding / spinal cord development / histone methyltransferase activity / positive regulation of stem cell population maintenance / G1/S-Specific Transcription / ATPase complex / Sin3-type complex / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / RNA Polymerase I Transcription Initiation / negative regulation of cell differentiation / histone deacetylase complex / G0 and Early G1 / subtelomeric heterochromatin formation / anatomical structure morphogenesis / heterochromatin / Cyclin E associated events during G1/S transition / nucleosome binding / Cyclin A:Cdk2-associated events at S phase entry / Deposition of new CENPA-containing nucleosomes at the centromere / enzyme activator activity / Regulation of TP53 Activity through Acetylation / methylated histone binding / SUMOylation of chromatin organization proteins / transcription corepressor binding / molecular condensate scaffold activity / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / negative regulation of cell migration / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / Defective pyroptosis / HDACs deacetylate histones / promoter-specific chromatin binding / hippocampus development / negative regulation of transforming growth factor beta receptor signaling pathway / cell cycle / heterochromatin formation / brain development / chromatin DNA binding / PKMTs methylate histone lysines / histone deacetylase binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / transcription corepressor activity / nucleosome assembly / chromosome / histone binding / methylation / Oxidative Stress Induced Senescence / DNA replication / cell population proliferation / Potential therapeutics for SARS / chromosome, telomeric region / nuclear body / ribonucleoprotein complex / chromatin remodeling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / chromatin / nucleolus / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||
![]() | Grau DJ / Armache KJ | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction. Authors: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas ...Authors: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz / Karim-Jean Armache / ![]() ![]() Abstract: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the ...Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin. Here, we present two cryo-EM structures of PRC2:EZH1, one as a monomer and a second one as a dimer bound to a nucleosome. When bound to nucleosome substrate, the PRC2:EZH1 dimer undergoes a dramatic conformational change. We demonstrate that mutation of a divergent EZH1/2 loop abrogates the nucleosome-binding and methyltransferase activities of PRC2:EZH1. Finally, we show that PRC2:EZH1 dimers are more effective than monomers at promoting chromatin compaction, and the divergent EZH1/2 loop is essential for this function, thereby tying together the methyltransferase, nucleosome-binding, and chromatin-compaction activities of PRC2:EZH1. We speculate that the conformational flexibility and the ability to dimerize enable PRC2 to act on the varied chromatin substrates it encounters in the cell. | |||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 95.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.7 KB 16.7 KB | Display Display | ![]() |
Images | ![]() | 146.1 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7ksrMC ![]() 7ksoC ![]() 7ktpC ![]() 7ktqC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | PRC2:EZH1_A from a dimeric PRC2 bound to a nucleosome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.35 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : PRC2:EZH1_A from a PRC2:EZH1 dimer bound to a nucleosome
Entire | Name: PRC2:EZH1_A from a PRC2:EZH1 dimer bound to a nucleosome |
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Components |
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-Supramolecule #1: PRC2:EZH1_A from a PRC2:EZH1 dimer bound to a nucleosome
Supramolecule | Name: PRC2:EZH1_A from a PRC2:EZH1 dimer bound to a nucleosome type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 266 KDa |
-Macromolecule #1: Histone-lysine N-methyltransferase EZH1
Macromolecule | Name: Histone-lysine N-methyltransferase EZH1 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: [histone H3]-lysine27 N-trimethyltransferase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 85.394141 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MEIPNPPTSK CITYWKRKVK SEYMRLRQLK RLQANMGAKA LYVANFAKVQ EKTQILNEEW KKLRVQPVQS MKPVSGHPFL KKCTIESIF PGFASQHMLM RSLNTVALVP IMYSWSPLQQ NFMVEDETVL CNIPYMGDEV KEEDETFIEE LINNYDGKVH G EEEMIPGS ...String: MEIPNPPTSK CITYWKRKVK SEYMRLRQLK RLQANMGAKA LYVANFAKVQ EKTQILNEEW KKLRVQPVQS MKPVSGHPFL KKCTIESIF PGFASQHMLM RSLNTVALVP IMYSWSPLQQ NFMVEDETVL CNIPYMGDEV KEEDETFIEE LINNYDGKVH G EEEMIPGS VLISDAVFLE LVDALNQYSD EEEEGHNDTS DGKQDDSKED LPVTRKRKRH AIEGNKKSSK KQFPNDMIFS AI ASMFPEN GVPDDMKERY RELTEMSDPN ALPPQCTPNI DGPNAKSVQR EQSLHSFHTL FCRRCFKYDC FLHPFHATPN VYK RKNKEI KIEPEPCGTD CFLLLEGAKE YAMLHNPRSK CSGRRRRRHH IVSASCSNAS ASAVAETKEG DSDRDTGNDW ASSS SEANS RCQTPTKQKA SPAPPQLCVV EAPSEPVEWT GAEESLFRVF HGTYFNNFCS IARLLGTKTC KQVFQFAVKE SLILK LPTD ELMNPSQKKK RKHRLWAAHC RKIQLKKDNS STQVYNYQPC DHPDRPCDST CPCIMTQNFC EKFCQCNPDC QNRFPG CRC KTQCNTKQCP CYLAVRECDP DLCLTCGASE HWDCKVVSCK NCSIQRGLKK HLLLAPSDVA GWGTFIKESV QKNEFIS EY CGELISQDEA DRRGKVYDKY MSSFLFNLNN DFVVDATRKG NKIRFANHSV NPNCYAKVVM VNGDHRIGIF AKRAIQAG E ELFFDYRYSQ ADALKYVGIE RETDVL UniProtKB: Histone-lysine N-methyltransferase EZH1 |
-Macromolecule #2: Histone-binding protein RBBP4
Macromolecule | Name: Histone-binding protein RBBP4 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 47.709527 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD FSIHRLVLGT HTSDEQNHLV IASVQLPND DAQFDASHYD SEKGEFGGFG SVSGKIEIEI KINHEGEVNR ARYMPQNPCI IATKTPSSDV LVFDYTKHPS K PDPSGECN ...String: MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD FSIHRLVLGT HTSDEQNHLV IASVQLPND DAQFDASHYD SEKGEFGGFG SVSGKIEIEI KINHEGEVNR ARYMPQNPCI IATKTPSSDV LVFDYTKHPS K PDPSGECN PDLRLRGHQK EGYGLSWNPN LSGHLLSASD DHTICLWDIS AVPKEGKVVD AKTIFTGHTA VVEDVSWHLL HE SLFGSVA DDQKLMIWDT RSNNTSKPSH SVDAHTAEVN CLSFNPYSEF ILATGSADKT VALWDLRNLK LKLHSFESHK DEI FQVQWS PHNETILASS GTDRRLNVWD LSKIGEEQSP EDAEDGPPEL LFIHGGHTAK ISDFSWNPNE PWVICSVSED NIMQ VWQMA ENIYNDEDPE GSVDPEGQGS UniProtKB: Histone-binding protein RBBP4 |
-Macromolecule #3: Polycomb protein SUZ12
Macromolecule | Name: Polycomb protein SUZ12 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 83.181922 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAPQKHGGGG GGGSGPSAGS GGGGFGGSAA VAAATASGGK SGGGSCGGGG SYSASSSSSA AAAAGAAVLP VKKPKMEHVQ ADHELFLQA FEKPTQIYRF LRTRNLIAPI FLHRTLTYMS HRNSRTNIKR KTFKVDDMLS KVEKMKGEQE SHSLSAHLQL T FTGFFHKN ...String: MAPQKHGGGG GGGSGPSAGS GGGGFGGSAA VAAATASGGK SGGGSCGGGG SYSASSSSSA AAAAGAAVLP VKKPKMEHVQ ADHELFLQA FEKPTQIYRF LRTRNLIAPI FLHRTLTYMS HRNSRTNIKR KTFKVDDMLS KVEKMKGEQE SHSLSAHLQL T FTGFFHKN DKPSPNSENE QNSVTLEVLL VKVCHKKRKD VSCPIRQVPT GKKQVPLNPD LNQTKPGNFP SLAVSSNEFE PS NSHMVKS YSLLFRVTRP GRREFNGMIN GETNENIDVN EELPARRKRN REDGEKTFVA QMTVFDKNRR LQLLDGEYEV AMQ EMEECP ISKKRATWET ILDGKRLPPF ETFSQGPTLQ FTLRWTGETN DKSTAPIAKP LATRNSESLH QENKPGSVKP TQTI AVKES LTTDLQTRKE KDTPNENRQK LRIFYQFLYN NNTRQQTEAR DDLHCPWCTL NCRKLYSLLK HLKLCHSRFI FNYVY HPKG ARIDVSINEC YDGSYAGNPQ DIHRQPGFAF SRNGPVKRTP ITHILVCRPK RTKASMSEFL ESEDGEVEQQ RTYSSG HNR LYFHSDTCLP LRPQEMEVDS EDEKDPEWLR EKTITQIEEF SDVNEGEKEV MKLWNLHVMK HGFIADNQMN HACMLFV EN YGQKIIKKNL CRNFMLHLVS MHDFNLISIM SIDKAVTKLR EMQQKLEKGE SASPANEEIT EEQNGTANGF SEINSKEK A LETDSVSGVS KQSKKQKL UniProtKB: Polycomb protein SUZ12 |
-Macromolecule #4: Polycomb protein EED
Macromolecule | Name: Polycomb protein EED / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 50.267691 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP NAPGRKSWGK GKWKSKKCKY SFKCVNSLK EDHNQPLFGV QFNWHSKEGD PLVFATVGSN RVTLYECHSQ GEIRLLQSYV DADADENFYT CAWTYDSNTS H PLLAVAGS ...String: MSEREVSTAP AGTDMPAAKK QKLSSDENSN PDLSGDENDD AVSIESGTNT ERPDTPTNTP NAPGRKSWGK GKWKSKKCKY SFKCVNSLK EDHNQPLFGV QFNWHSKEGD PLVFATVGSN RVTLYECHSQ GEIRLLQSYV DADADENFYT CAWTYDSNTS H PLLAVAGS RGIIRIINPI TMQCIKHYVG HGNAINELKF HPRDPNLLLS VSKDHALRLW NIQTDTLVAI FGGVEGHRDE VL SADYDLL GEKIMSCGMD HSLKLWRINS KRMMNAIKES YDYNPNKTNR PFISQKIHFP DFSTRDIHRN YVDCVRWLGD LIL SKSCEN AIVCWKPGKM EDDIDKIKPS ESNVTILGRF DYSQCDIWYM RFSMDFWQKM LALGNQVGKL YVWDLEVEDP HKAK CTTLT HHKCGAAIRQ TSFSRDSSIL IAVCDDASIW RWDRLR UniProtKB: Polycomb protein EED |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 7 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.12 mg/mL | |||||||||||||||
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Buffer | pH: 7.9 Component:
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 56.7 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |