Activation of automethylated PRC2 by dimerization on chromatin.

chromatin cryo-EM development epigenetics gene regulation

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
13 Oct 2023
Historique:
pubmed: 24 10 2023
medline: 24 10 2023
entrez: 24 10 2023
Statut: epublish

Résumé

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 EZH2 stimulates its activity by an unknown mechanism. Here, we show that 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

Identifiants

DOI: 10.1101/2023.10.12.562141 PMID: 37873121 PMC: PMC10592840
pubmed: 37873121
doi: 10.1101/2023.10.12.562141
pmc: PMC10592840
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM129325
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM127018
Pays : United States

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing interests.

Auteurs

Paul V Sauer (PV)

California Institute for Quantitative Biology (QB3), University of California, Berkeley, California 94720, USA.
Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.

Egor Pavlenko (E)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.

Trinity Cookis (T)

Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.

Linda C Zirden (LC)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.

Juliane Renn (J)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.

Ankush Singhal (A)

Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory.

Pascal Hunold (P)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.
Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.

Michaela N Hoehne (MN)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.
Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.

Olivia van Ray (O)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.
Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.

Robert Hänsel-Hertsch (R)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.
Department of Translational Genomics, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931, Cologne, Germany.
Institute of Human Genetics, University Hospital Cologne, 50931 Cologne, Germany.
Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Germany.

Karissa Y Sanbonmatsu (KY)

Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory.

Eva Nogales (E)

California Institute for Quantitative Biology (QB3), University of California, Berkeley, California 94720, USA.
Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.

Simon Poepsel (S)

Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital, University of Cologne, Germany.
Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, Germany.

Classifications MeSH