EMD-11910

Single-particle
4.4 Å
EMD-11910 Deposition: 29/10/2020
Map released: 09/12/2020
Last modified: 01/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-11910

Histone H3 recognition by nucleosome-bound PRC2 subunit EZH2.

EMD-11910

Single-particle
4.4 Å
EMD-11910 Deposition: 29/10/2020
Map released: 09/12/2020
Last modified: 01/05/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Xenopus laevis, Homo sapiens, synthetic construct
Sample: EM map of EZH2 on nucleosome obtained from signal particle subtraction and focused refinement on PHF1-PRC2:dinucleosome map.
Fitted models: 7at8 (Avg. Q-score: 0.29)

Deposition Authors: Finogenova K , Benda C
Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3.
PUBMED: 33211010
DOI: doi:10.7554/eLife.61964
ISSN: 2050-084X
Abstract:
Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface. Mutation of H3K36 to arginine or alanine inhibits H3K27 methylation by PRC2 on nucleosomes in vitro. Accordingly, Drosophila H3K36A and H3K36R mutants show reduced levels of H3K27me3 and defective Polycomb repression of HOX genes. The relay of interactions between EZH2, the nucleosomal DNA and the H3 N-terminus therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in transcriptionally active chromatin.