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TitleStructural mechanism of HP1⍺-dependent transcriptional repression and chromatin compaction.
Journal, issue, pagesStructure, Vol. 32, Issue 11, Page 2094-22106.e6, Year 2024
Publish dateNov 7, 2024
AuthorsVladyslava Sokolova / Jacob Miratsky / Vladimir Svetlov / Michael Brenowitz / John Vant / Tyler S Lewis / Kelly Dryden / Gahyun Lee / Shayan Sarkar / Evgeny Nudler / Abhishek Singharoy / Dongyan Tan /
PubMed AbstractHeterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their ...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.
External linksStructure / PubMed:39383876 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 6.6 Å
Structure data

EMDB-42690: Heterochromatin protein 1 (HP1) alpha in complex with an H2A.Z nucleosome(focused refined map)
Method: EM (single particle) / Resolution: 6.6 Å

EMDB-42692: K9me3-H2A.Z nucleosome from focus refinement of the HP1-H2A.Z nucleosome complex
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-42773: structure of the K9me3-H2A.Z nucleosome
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-42774, PDB-8uxq:
Structure of Heterochromatin Protein 1 (HP1) alpha in complex with an H2A.Z nucleosome
Method: EM (single particle) / Resolution: 6.3 Å

Source
  • Escherichia coli (E. coli)
  • xenopus laevis (African clawed frog)
  • mus musculus (house mouse)
  • synthetic construct (others)
  • homo sapiens (human)
KeywordsSTRUCTURAL PROTEIN / heterochromatin / nucleosome / chromatin / GENE REGULATION

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