Molecular Cell

, volume 84 , issue 20 , pages 3885-3898.e8

Activation of automethylated PRC2 by dimerization on chromatin

Paul V Sauer ¹

Egor Pavlenko ²

Trinity Cookis ³

Linda C Zirden ²

Juliane Renn ²

Ankush Singhal ⁴

Pascal Hunold ⁵

Michaela N. Hoehne-Wiechmann ⁵

Olivia Van Ray ⁵

Farnusch Kaschani ⁶

Markus Kaiser ⁶

Robert Hänsel Hertsch ⁷

K. Sanbonmatsu ⁴

Eva Nogales ⁸

Simon Poepsel ⁹

Hide authors affiliations Show authors affiliations: 9 affiliations

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

University of California, Berkeley

Howard Hughes Medical Institute

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

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

⁴

Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. |

⁵

⁶

Department of Chemical Biology, University of Duisburg-Essen, Center for Medical Biotechnology (ZMB), Faculty of Biology, Essen, Germany. |

⁷

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 Genetics, University Hospital Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. |

⁸

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 Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: enogales@lbl.gov.

Lawrence Berkeley National Laboratory

University of California, Berkeley

Howard Hughes Medical Institute

⁹

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: spoepsel@uni-koeln.de. |

Publication type: Journal Article

Publication date: 2024-10-01

Elsevier

Molecular Cell

scimago Q1

wos Q1

SJR: 9.051

CiteScore: 24.4

Impact factor: 16.6

ISSN: 10972765, 10974164

DOI: 10.1016/j.molcel.2024.08.025

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PubMed ID: 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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Sauer P. V. et al. Activation of automethylated PRC2 by dimerization on chromatin // Molecular Cell. 2024. Vol. 84. No. 20. p. 3885-3898.e8.

GOST all authors (up to 50) Copy

Sauer P. V., Pavlenko E., Cookis T., Zirden L. C., Renn J., Singhal A., Hunold P., Hoehne-Wiechmann M. N., Van Ray O., Kaschani F., Kaiser M., Hänsel Hertsch R., Sanbonmatsu K., Nogales E., Poepsel S. Activation of automethylated PRC2 by dimerization on chromatin // Molecular Cell. 2024. Vol. 84. No. 20. p. 3885-3898.e8.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1016/j.molcel.2024.08.025

UR - https://linkinghub.elsevier.com/retrieve/pii/S1097276524007020

TI - Activation of automethylated PRC2 by dimerization on chromatin

T2 - Molecular Cell

AU - Sauer, Paul V

AU - Pavlenko, Egor

AU - Cookis, Trinity

AU - Zirden, Linda C

AU - Renn, Juliane

AU - Singhal, Ankush

AU - Hunold, Pascal

AU - Hoehne-Wiechmann, Michaela N.

AU - Van Ray, Olivia

AU - Kaschani, Farnusch

AU - Kaiser, Markus

AU - Hänsel Hertsch, Robert

AU - Sanbonmatsu, K.

AU - Nogales, Eva

AU - Poepsel, Simon

PY - 2024

DA - 2024/10/01

PB - Elsevier

SP - 3885-3898.e8

IS - 20

VL - 84

PMID - 39303719

SN - 1097-2765

SN - 1097-4164

ER -

BibTex |

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BibTex (up to 50 authors) Copy

@article{2024_Sauer,

author = {Paul V Sauer and Egor Pavlenko and Trinity Cookis and Linda C Zirden and Juliane Renn and Ankush Singhal and Pascal Hunold and Michaela N. Hoehne-Wiechmann and Olivia Van Ray and Farnusch Kaschani and Markus Kaiser and Robert Hänsel Hertsch and K. Sanbonmatsu and Eva Nogales and Simon Poepsel},

title = {Activation of automethylated PRC2 by dimerization on chromatin},

journal = {Molecular Cell},

year = {2024},

volume = {84},

publisher = {Elsevier},

month = {oct},

url = {https://linkinghub.elsevier.com/retrieve/pii/S1097276524007020},

number = {20},

pages = {3885--3898.e8},

doi = {10.1016/j.molcel.2024.08.025}

}

MLA

Cite this

MLA Copy

Sauer, Paul V., et al. “Activation of automethylated PRC2 by dimerization on chromatin.” Molecular Cell, vol. 84, no. 20, Oct. 2024, pp. 3885-3898.e8. https://linkinghub.elsevier.com/retrieve/pii/S1097276524007020.

Publisher

Elsevier

Journal

Molecular Cell

scimago Q1

wos Q1

SJR

9.051

CiteScore

24.4

Impact factor

16.6

ISSN

10972765 (Print)

10974164 (Electronic)