RYBP-PRC1 的组蛋白泛素化读写机制的结构基础。

Laboratory of Chromatin Biology, Max-Planck Institute of Biochemistry, Martinsried, Germany.

Department of Structural Cell Biology, Max-Planck Institute of Biochemistry, Martinsried, Germany.

Nat Struct Mol Biol. 2024 Jul;31(7):1023-1027. doi: 10.1038/s41594-024-01258-x. Epub 2024 Mar 25.

Histone H2A monoubiquitination (H2Aub1) by the PRC1 subunit RING1B entails a positive feedback loop, mediated by the RING1B-interacting protein RYBP. We uncover that human RYBP-PRC1 binds unmodified nucleosomes via RING1B but H2Aub1-modified nucleosomes via RYBP. RYBP interactions with both ubiquitin and the nucleosome acidic patch create the high binding affinity that favors RYBP- over RING1B-directed PRC1 binding to H2Aub1-modified nucleosomes; this enables RING1B to monoubiquitinate H2A in neighboring unmodified nucleosomes.

组蛋白 H2A 单泛素化 (H2Aub1) 由 PRC1 亚基 RING1B 完成，涉及一个正反馈回路，由 RING1B 相互作用蛋白 RYBP 介导。我们揭示了人 RYBP-PRC1 通过 RING1B 结合未修饰核小体，但通过 RYBP 结合 H2Aub1 修饰核小体。RYBP 与泛素和核小体酸性斑的相互作用创造了高结合亲和力，有利于 RYBP-而非 RING1B 指导的 PRC1 结合到 H2Aub1 修饰核小体上；这使得 RING1B 能够在相邻未修饰核小体上单泛素化 H2A。