Structural and functional analysis of the SET3 histone deacetylase complex

The SET3 complex (SET3C) is a seven‐subunit histone deacetylase complex that is capable of transcriptional regulation. Methylated histone 3 marks recruit SET3C to the nucleosome, and the SET3C catalytic subunits deacetylate the histone 3 and 4 tails. There is very limited structural knowledge of the SET3C subunits, with most subunits having unknown structures or functions. Here, a catalytically active SET3 complex was endogenously purified from Saccharomyces cerevisiae and utilized for negative‐stain electron microscopy (EM) to determine an apo model for the holo complex. The negative‐stain EM 3D model revealed a three‐lobe architecture, with each lobe extending from a central point. An electron‐microscopy model of the SET3 histone deacetylase complex reveals a three‐lobe architecture.