Structures and dynamics of Rpd3S complex bound to nucleosome

TL;DR

Researchers reveal the structure and movement of the Rpd3S complex when bound to nucleosomes, showing how it targets different sites for histone deacetylation.

Contribution

The study provides atomic-resolution cryo-EM structures of the Rpd3S complex in multiple nucleosome-bound states, revealing its dynamic engagement with nucleosomes.

Findings

The Rpd3S complex has a rigid core with three positively charged anchors that bind nucleosomal DNA.

The Rpd3S complex adopts three distinct orientations relative to the nucleosome to target different deacetylation sites.

Structures show how the Rpd3S complex accommodates a mononucleosome without linker DNA.

Abstract

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.

Structures of the Rpd3S complex bound to native nucleosome reveal a dynamic working model to engage diverse deacetylation sites.

Figures