{"doi":"10.1016/j.jbc.2021.101558","title":"A capped Tudor domain within a core subunit of the Sin3L/Rpd3L histone deacetylase complex binds to nucleic acid G-quadruplexes","abstract":"Chromatin-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 posttranslational 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 Sin3L/Rpd3L complex, harbors a type of Tudor domain that we designate the capped Tudor domain. Unlike canonical Tudor domains that bind modified histones, the Sds3 capped Tudor domain 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 that was previously shown to bind single-stranded RNA. Our findings expand the range of macromolecules capable of recruiting the Sin3L/Rpd3L complex and draw attention to potentially new biological roles for this HDAC complex. Chromatin-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 posttranslational 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 Sin3L/Rpd3L complex, harbors a type of Tudor domain that we designate the capped Tudor domain. Unlike canonical Tudor domains that bind modified histones, the Sds3 capped Tudor domain 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 that was previously shown to bind single-stranded RNA. Our findings expand the range of macromolecules capable of recruiting the Sin3L/Rpd3L complex and draw attention to potentially new biological roles for this HDAC complex. Posttranslational modifications of core histones constitute a common molecular mechanism for regulating transcription by modulating DNA template accessibility to RNA polymerases, regulatory factors, and other effectors (1Gardner K.E. Allis C.D. Strahl B.D. Operating on chromatin, a colorful language where context matters.J. Mol. Biol. 2011; 409: 36-46Google Scholar, 2Bowman G.D. Poirier M.G. Post-translational modifications of histones that influence nucleosome dynamics.Chem. Rev. 2015; 115: 2274-2295Google Scholar). Among various posttranslational modifications, acetylation of lysine residues is not only abundant but also one that is characterized by high turnover, consistent with its central role in the dynamic induction and repression of genes (3Evertts A.G. Zee B.M. Dimaggio P.A. Gonzales-Cope M. Coller H.A. Garcia B.A. Quantitative dynamics of the link between cellular metabolism and histone acetylation.J. Biol. Chem. 2013; 288: 12142-12151Google Scholar). Deacetylation of histones in mammals is mediated in large part by histone deacetylases (HDACs) 1, 2, and 3 (4Moser M.A. Hagelkruys A. Seiser C. Transcription and beyond: The role of mammalian class I lysine deacetylases.Chromosoma. 2014; 123: 67-78Google Scholar, 5Yan","journal":"Journal of Biological Chemistry","year":2022,"id":277467,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":828730,"name":"Joseph Hsieh","orcid":"0000-0002-3828-2192","position":1,"is_corresponding":false},{"id":829036,"name":"Maksim Giljen","orcid":null,"position":2,"is_corresponding":false},{"id":949552,"name":"Emily Justice","orcid":null,"position":3,"is_corresponding":false},{"id":949068,"name":"Nicolas Daffern","orcid":"0009-0006-6596-8612","position":4,"is_corresponding":false},{"id":706257,"name":"Yongbo Zhang","orcid":"0000-0002-8216-1371","position":5,"is_corresponding":false},{"id":64914,"name":"Ishwar Radhakrishnan","orcid":"0000-0002-0195-9710","position":6,"is_corresponding":false},{"id":531915,"name":"Ryan Marcum","orcid":"0000-0002-4595-8023","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T00:28:39.226969Z","pmid":"34979096","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}