Summary for 8T9G
| Entry DOI | 10.2210/pdb8t9g/pdb |
| EMDB information | 41110 |
| Descriptor | Polycomb protein SUZ12, Histone H2B 1.1, DNA (226-MER), ... (13 entities in total) |
| Functional Keywords | histone methyl transferase, gene repression, epigenetics, chromatin, gene regulation |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 21 |
| Total formula weight | 825687.67 |
| Authors | Sauer, P.V.,Pavlenko, E.,Nogales, E.,Poepsel, S. (deposition date: 2023-06-23, release date: 2024-09-25, Last modification date: 2024-11-06) |
| Primary citation | 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.,Hansel-Hertsch, R.,Sanbonmatsu, K.Y.,Nogales, E.,Poepsel, S. Activation of automethylated PRC2 by dimerization on chromatin. Mol.Cell, 84:3885-3898.e8, 2024 Cited by PubMed 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. PubMed: 39303719DOI: 10.1016/j.molcel.2024.08.025 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (6.2 Å) |
Structure validation
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