A Capped Tudor Domain within a Core Subunit of the Sin3L/Rpd3L Histone Deacetylase Complex Binds Nucleic Acids

Abstract

AbstractChromatin-modifying complexes containing histone deacetylase (HDAC) activities play critical roles in the regulation of gene transcription in eukaryotes. These complexes are thought to lack intrinsic DNA-binding activity, but according to a well-established paradigm, they are recruited via protein-protein interactions by gene-specific transcription factors and post-translational histone modifications to their sites of action on the genome. The mammalian Sin3L/Rpd3L complex, comprising more than a dozen different polypeptides, is an ancient HDAC complex found in diverse eukaryotes. The subunits of this complex harbor conserved domains and motifs of unknown structure and function. Here we show that Sds3, a constitutively associated subunit critical for the proper functioning of the complex, harbors a type of Tudor domain that we designate the capped Tudor domain (CTD). Unlike canonical Tudor domains that bind modified histones, the Sds3 CTD binds to nucleic acids that can form higher-order structures such as G-quadruplexes, and shares similarities with the knotted Tudor domain of the Esa1 histone acetyltransferase (HAT) that was previously shown to bind single-stranded RNA. Our findings expand the range of macromolecules capable of recruiting the Sin3L/Rpd3L complex and draws attention to potentially new roles for this HDAC complex in transcription biology.