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Activation of automethylated PRC2 by dimerization on chromatin.
Sauer, Paul V; Pavlenko, Egor; Cookis, Trinity; Zirden, Linda C; Renn, Juliane; Singhal, Ankush; Hunold, Pascal; Hoehne-Wiechmann, Michaela N; van Ray, Olivia; Kaschani, Farnusch; Kaiser, Markus; Hänsel-Hertsch, Robert; Sanbonmatsu, Karissa Y; Nogales, Eva; Poepsel, Simon.
Afiliação
  • Sauer PV; California Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
  • Pavlenko E; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany.
  • Cookis T; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
  • Zirden LC; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany.
  • Renn J; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany.
  • Singhal A; Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  • Hunold P; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Hoehne-Wiechmann MN; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • van Ray O; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
  • Kaschani F; Department of Chemical Biology, University of Duisburg-Essen, Center for Medical Biotechnology (ZMB), Faculty of Biology, Essen, Germany.
  • Kaiser M; Department of Chemical Biology, University of Duisburg-Essen, Center for Medical Biotechnology (ZMB), Faculty of Biology, Essen, Germany.
  • Hänsel-Hertsch R; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Institute of Human Genet
  • Sanbonmatsu KY; Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  • Nogales E; California Institute for Quantitative Biology (QB3), University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Molecular Biophysic
  • Poepsel S; Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. Electronic address:
Mol Cell ; 84(20): 3885-3898.e8, 2024 Oct 17.
Article em En | MEDLINE | ID: mdl-39303719
ABSTRACT
Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that trimethylates lysine 27 of histone 3 (H3K27me3) and is essential for embryonic development and cellular differentiation. H3K27me3 is associated with transcriptionally repressed chromatin and is established when PRC2 is allosterically activated upon methyl-lysine binding by the regulatory subunit EED. Automethylation of the catalytic subunit enhancer of zeste homolog 2 (EZH2) stimulates its activity by an unknown mechanism. Here, we show that human PRC2 forms a dimer on chromatin in which an inactive, automethylated PRC2 protomer is the allosteric activator of a second PRC2 that is poised to methylate H3 of a substrate nucleosome. Functional assays support our model of allosteric trans-autoactivation via EED, suggesting a previously unknown mechanism mediating context-dependent activation of PRC2. Our work showcases the molecular mechanism of auto-modification-coupled dimerization in the regulation of chromatin-modifying complexes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Histonas / Multimerização Proteica / Complexo Repressor Polycomb 2 / Proteína Potenciadora do Homólogo 2 de Zeste Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Histonas / Multimerização Proteica / Complexo Repressor Polycomb 2 / Proteína Potenciadora do Homólogo 2 de Zeste Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article