Structures and dynamics of Rpd3S complex bound to nucleosome

Sci Adv. 2024 Apr 12;10(15):eadk7678. doi: 10.1126/sciadv.adk7678. Epub 2024 Apr 10.


The Rpd3S complex plays a pivotal role in facilitating local histone deacetylation in the transcribed regions to suppress intragenic transcription initiation. Here, we present the cryo-electron microscopy structures of the budding yeast Rpd3S complex in both its apo and three nucleosome-bound states at atomic resolutions, revealing the exquisite architecture of Rpd3S to well accommodate a mononucleosome without linker DNA. The Rpd3S core, containing a Sin3 Lobe and two NB modules, is a rigid complex and provides three positive-charged anchors (Sin3_HCR and two Rco1_NIDs) to connect nucleosomal DNA. In three nucleosome-bound states, the Rpd3S core exhibits three distinct orientations relative to the nucleosome, assisting the sector-shaped deacetylase Rpd3 to locate above the SHL5-6, SHL0-1, or SHL2-3, respectively. Our work provides a structural framework that reveals a dynamic working model for the Rpd3S complex to engage diverse deacetylation sites.

MeSH terms

  • Cryoelectron Microscopy
  • DNA / metabolism
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Methylation
  • Nucleosomes*
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism


  • Nucleosomes
  • Histones
  • Histone Deacetylases
  • DNA
  • Saccharomyces cerevisiae Proteins