Structural basis for the regulation of nucleosome recognition and HDAC activity by histone deacetylase assemblies

Sci Adv. 2021 Jan 8;7(2):eabd4413. doi: 10.1126/sciadv.abd4413. Print 2021 Jan.


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 Hda12-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism
  • Cryoelectron Microscopy
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Nucleosomes* / metabolism
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism


  • Chromatin
  • Histones
  • Nucleosomes
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • HDA1 protein, S cerevisiae
  • Histone Deacetylases