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TitleStructural basis for the regulation of nucleosome recognition and HDAC activity by histone deacetylase assemblies.
Journal, issue, pagesSci Adv, Vol. 7, Issue 2, Year 2021
Publish dateJan 8, 2021
AuthorsJung-Hoon Lee / Daniel Bollschweiler / Tillman Schäfer / Robert Huber /
PubMed AbstractThe chromatin-modifying histone deacetylases (HDACs) remove acetyl groups from acetyl-lysine residues in histone amino-terminal tails, thereby mediating transcriptional repression. Structural makeup ...The chromatin-modifying histone deacetylases (HDACs) remove acetyl groups from acetyl-lysine residues in histone amino-terminal tails, thereby mediating transcriptional repression. Structural makeup and mechanisms by which multisubunit HDAC complexes recognize nucleosomes remain elusive. Our cryo-electron microscopy structures of the yeast class II HDAC ensembles show that the HDAC protomer comprises a triangle-shaped assembly of stoichiometry Hda1-Hda2-Hda3, in which the active sites of the Hda1 dimer are freely accessible. We also observe a tetramer of protomers, where the nucleosome binding modules are inaccessible. Structural analysis of the nucleosome-bound complexes indicates how positioning of Hda1 adjacent to histone H2B affords HDAC catalysis. Moreover, it reveals how an intricate network of multiple contacts between a dimer of protomers and the nucleosome creates a platform for expansion of the HDAC activities. Our study provides comprehensive insight into the structural plasticity of the HDAC complex and its functional mechanism of chromatin modification.
External linksSci Adv / PubMed:33523989 / PubMed Central
MethodsEM (single particle)
Resolution3.11 - 10.6 Å
Structure data

EMDB-11092, PDB-6z6f:
HDAC-PC
Method: EM (single particle) / Resolution: 3.11 Å

EMDB-11094, PDB-6z6h:
HDAC-DC
Method: EM (single particle) / Resolution: 8.55 Å

EMDB-11101, PDB-6z6o:
HDAC-TC
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-11102, PDB-6z6p:
HDAC-PC-Nuc
Method: EM (single particle) / Resolution: 4.43 Å

EMDB-11712:
HDAC-DC-nucleosome
Method: EM (single particle) / Resolution: 10.6 Å

EMDB-11797:
HDAC-PC bound to nucleosome
Method: EM (single particle) / Resolution: 4.37 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
  • xenopus laevis (African clawed frog)
  • unidentified plasmid (others)
KeywordsGENE REGULATION / Protein complex

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