EMD-41110
Automethylated PRC2 dimer bound to nucleosome
EMD-41110
Single-particle6.2 Å
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Map released: 25/09/2024
Last modified: 06/11/2024
Sample Organism:
Homo sapiens,
Xenopus laevis,
synthetic construct
Sample: Automethylated PRC2 dimer bound to nucleosome
Fitted models: 8t9g (Avg. Q-score: 0.163)
Raw data: EMPIAR-11607
Deposition Authors: Sauer PV, Pavlenko E, Nogales E, Poepsel S
Sample: Automethylated PRC2 dimer bound to nucleosome
Fitted models: 8t9g (Avg. Q-score: 0.163)
Raw data: EMPIAR-11607
Deposition Authors: Sauer PV, Pavlenko E, Nogales E, Poepsel S
Activation of automethylated PRC2 by dimerization on chromatin.
Sauer PV,
Pavlenko E,
Cookis T,
Zirden LC,
Renn J,
Singhal A,
Hunold P,
Hoehne-Wiechmann MN,
van Ray O,
Kaschani F,
Kaiser M,
Hansel-Hertsch R,
Sanbonmatsu KY,
Nogales E,
Poepsel S
(2024) Mol Cell , 84 , 3885 - 3898.e8
(2024) Mol Cell , 84 , 3885 - 3898.e8
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.
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.