8UXQ

Structure of Heterochromatin Protein 1 (HP1) alpha in complex with an H2A.Z nucleosome

Summary for 8UXQ

• Entry DOI: 10.2210/pdb8uxq/pdb
• EMDB information: 42774
• Descriptor: Chromobox protein homolog 5, Histone H3.2, Histone H4, ... (7 entities in total)
• Functional Keywords: heterochromatin, nucleosome, chromatin, gene regulation, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 281479.26

Authors

Tan, D.,Sokolova, V. (deposition date: 2023-11-09, release date: 2024-09-25, Last modification date: 2025-04-09)

Primary citation

Sokolova, V.,Miratsky, J.,Svetlov, V.,Brenowitz, M.,Vant, J.,Lewis, T.S.,Dryden, K.,Lee, G.,Sarkar, S.,Nudler, E.,Singharoy, A.,Tan, D.
Structural mechanism of HP1⍺-dependent transcriptional repression and chromatin compaction.
Structure, 32:2094-2106.e6, 2024

PubMed Abstract: Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their contributions to heterochromatin functions remain elusive. Here, we present the cryoelectron microscopy (cryo-EM) structure of an HP1α dimer bound to an H2A.Z-nucleosome, revealing two distinct HP1α-nucleosome interfaces. The primary HP1α binding site is located at the N terminus of histone H3, specifically at the trimethylated lysine 9 (K9me3) region, while a secondary binding site is situated near histone H2B, close to nucleosome superhelical location 4 (SHL4). Our biochemical data further demonstrates that HP1α binding influences the dynamics of DNA on the nucleosome. It promotes DNA unwrapping near the nucleosome entry and exit sites while concurrently restricting DNA accessibility in the vicinity of SHL4. Our study offers a model for HP1α-mediated heterochromatin maintenance and gene silencing. It also sheds light on the H3K9me-independent role of HP1 in responding to DNA damage.

PubMed: 39383876
DOI: 10.1016/j.str.2024.09.013

Experimental method

ELECTRON MICROSCOPY (6.3 Å)