Structures and dynamics of Rpd3S complex bound to nucleosome.

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.

Two assembly modes for SIN3 histone deacetylase complexes.

The switch-independent 3 (SIN3)/histone deacetylase (HDAC) complexes play essential roles in regulating chromatin accessibility and gene expression. There are two major types of SIN3/HDAC complexes (named SIN3L and SIN3S) targeting different chromatin regions. Here we present the cryo-electron microscopy structures of the SIN3L and SIN3S complexes from Schizosaccharomyces pombe (S. pombe), revealing two distinct assembly modes. In the structure of SIN3L, each Sin3 isoform (Pst1 and Pst3) interacts with one histone deacetylase Clr6, and one WD40-containing protein Prw1, forming two lobes. These two lobes are bridged by two vertical coiled-coil domains from Sds3/Dep1 and Rxt2/Png2, respectively. In the structure of SIN3S, there is only one lobe organized by another Sin3 isoform Pst2; each of the Cph1 and Cph2 binds to an Eaf3 molecule, providing two modules for histone recognition and binding. Notably, the Pst1 Lobe in SIN3L and the Pst2 Lobe in SIN3S adopt similar conformation with their deacetylase active sites exposed to the space; however, the Pst3 Lobe in SIN3L is in a compact state with its active center buried inside and blocked. Our work reveals two classical organization mechanisms for the SIN3/HDAC complexes to achieve specific targeting and provides a framework for studying the histone deacetylase complexes.

Structure of a SIN3-HDAC complex from budding yeast.

SIN3-HDAC (histone deacetylases) complexes have important roles in facilitating local histone deacetylation to regulate chromatin accessibility and gene expression. Here, we present the cryo-EM structure of the budding yeast SIN3-HDAC complex Rpd3L at an average resolution of 2.6 Å. The structure reveals that two distinct arms (ARM1 and ARM2) hang on a T-shaped scaffold formed by two coiled-coil domains. In each arm, Sin3 interacts with different subunits to create a different environment for the histone deacetylase Rpd3. ARM1 is in the inhibited state with the active site of Rpd3 blocked, whereas ARM2 is in an open conformation with the active site of Rpd3 exposed to the exterior space. The observed asymmetric architecture of Rpd3L is different from those of available structures of other class I HDAC complexes. Our study reveals the organization mechanism of the SIN3-HDAC complex and provides insights into the interaction pattern by which it targets histone deacetylase to chromatin.

Author Correction: Structure of the yeast Swi/Snf complex in a nucleosome free state.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Structure of the yeast Swi/Snf complex in a nucleosome free state.

SWI/SNF remodelers play a key role in regulating chromatin architecture and gene expression. Here, we report the cryo-EM structure of the Saccharomyces cerevisiae Swi/Snf complex in a nucleosome-free state. The structure consists of a stable triangular base module and a flexible Arp module. The conserved subunits Swi1 and Swi3 form the backbone of the complex and closely interact with other components. Snf6, which is specific for yeast Swi/Snf complex, stabilizes the binding of the ATPase-containing subunit Snf2 to the base module. Comparison of the yeast Swi/Snf and RSC complexes reveals conserved structural features that govern the assembly and function of these two subfamilies of chromatin remodelers. Our findings complement those from recent structures of the yeast and human chromatin remodelers and provide further insights into the assembly and function of the SWI/SNF remodelers.