EMD-41110

Single-particle
6.2 Å
EMD-41110 Deposition: 23/06/2023
Map released: 25/09/2024
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-41110

Automethylated PRC2 dimer bound to nucleosome

EMD-41110

Single-particle
6.2 Å
EMD-41110 Deposition: 23/06/2023
Map released: 25/09/2024
Last modified: 06/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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
Activation of automethylated PRC2 by dimerization on chromatin.
PUBMED: 39303719
DOI: doi:10.1016/j.molcel.2024.08.025
ISSN: 1097-2765
ASTM: MOCEFL
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.