9DGG

ncPRC1RYBP bound to unmodified nucleosome

Summary for 9DGG

• Entry DOI: 10.2210/pdb9dgg/pdb
• EMDB information: 46823
• Descriptor: Histone H3.2, Histone H4, Histone H2A type 1, ... (9 entities in total)
• Functional Keywords: dna complex protein, nuclear protein-dna complex, nuclear protein/dna
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 12
• Total formula weight: 300250.10

Authors

Godinez-Lopez, V.,Valencia-Sanchez, M.I.,Armache, J.P.,Armache, K.-J. (deposition date: 2024-09-02, release date: 2024-11-20, Last modification date: 2025-01-15)

Primary citation

Lopez, V.G.,Valencia-Sanchez, M.I.,Abini-Agbomson, S.,Thomas, J.F.,Lee, R.,De Ioannes, P.,Sosa, B.A.,Armache, J.P.,Armache, K.J.
Read-write mechanisms of H2A ubiquitination by Polycomb repressive complex 1.
Nature, 636:755-761, 2024

PubMed Abstract: Epigenetic inheritance of silent chromatin domains is fundamental to cellular memory during embryogenesis, but it must overcome the dilution of repressive histone modifications during DNA replication. One such modification, histone H2A lysine 119 monoubiquitination (H2AK119Ub), needs to be re-established by the Polycomb repressive complex 1 (PRC1) E3 ligase to restore the silent Polycomb domain. However, the exact mechanism behind this restoration remains unknown. Here, combining cryo-electron microscopy (cryo-EM) and functional approaches, we characterize the read-write mechanism of the non-canonical PRC1-containing RYBP (ncPRC1). This mechanism, which functions as a positive-feedback loop in epigenetic regulation, emphasizes the pivotal role of ncPRC1 in restoring H2AK119Ub. We observe an asymmetrical binding of ncPRC1 to H2AK119Ub nucleosomes, guided in part by the N-terminal zinc-finger domain of RYBP binding to residual H2AK119Ub on nascent chromatin. This recognition positions the RING domains of RING1B and BMI1 on the unmodified nucleosome side, enabling recruitment of the E2 enzyme to ubiquitinate H2AK119 within the same nucleosome (intra-nucleosome read-write) or across nucleosomes (inter-nucleosome read-write). Collectively, our findings provide key structural and mechanistic insights into the dynamic interplay of epigenetic regulation, highlighting the significance of ncPRC1 in H2AK119Ub restoration to sustain repressive chromatin domains.

PubMed: 39537923
DOI: 10.1038/s41586-024-08183-5

Experimental method

ELECTRON MICROSCOPY (2.98 Å)