EMD-43363

Single-particle
3.3 Å
EMD-43363 Deposition: 14/01/2024
Map released: 22/01/2025
Last modified: 22/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-43363

H3K36me3-modified nucleosome bound to PRC2_AJ1-450 with histone H3 tail disengaged

EMD-43363

Single-particle
3.3 Å
EMD-43363 Deposition: 14/01/2024
Map released: 22/01/2025
Last modified: 22/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Xenopus laevis
Sample: H3K36me3 modified nucleosome core particle
Fitted models: 8vo0 (Avg. Q-score: 0.258)

Deposition Authors: Cookis T, Nogales E
Structural basis for the inhibition of PRC2 by active transcription histone posttranslational modifications.
Cookis T, Lydecker A, Sauer P , Kasinath V, Nogales E
(2025) Nat Struct Mol Biol
PUBMED: 39774834
DOI: doi:10.1038/s41594-024-01452-x
ISSN: 1545-9985
Abstract:
Polycomb repressive complex 2 (PRC2) trimethylates histone H3 on K27 (H3K27me3) leading to gene silencing that is essential for embryonic development and maintenance of cell identity. PRC2 is regulated by protein cofactors and their crosstalk with histone modifications. Trimethylated histone H3 on K4 (H3K4me3) and K36 (H3K36me3) localize to sites of active transcription and inhibit PRC2 activity through unknown mechanisms. Using cryo-electron microscopy, we reveal that histone H3 tails containing H3K36me3 engage poorly with PRC2 and preclude its effective interaction with chromatin, while H3K4me3 binds to the allosteric site in the EED subunit, acting as an antagonist that competes with activators required for spreading of the H3K27me3 repressive mark. Thus, the location of the H3K4me3 and H3K36me3 modifications along the H3 tail allows them to target two requirements for efficient trimethylation of H3K27 by PRC2. We further show that the JARID2 cofactor modulates PRC2 activity in the presence of these histone modifications.