{"doi":"10.1371/journal.pbio.3003059","title":"H2A.Z deposition by the SWR complex is stimulated by polyadenine DNA sequences in nucleosomes","abstract":"The variant histone H2A.Z is deposited into nucleosomes immediately downstream of promoters, where it plays a critical role in transcription. The site-specific deposition of H2A.Z is catalyzed by the SWR complex, a conserved chromatin remodeler with affinity for promoter-proximal nucleosome-depleted regions (NDRs) and histone acetylation. By comparing the genomic distribution of H2A.Z in wild-type and SWR-deficient cells, we found that SWR is also responsible for depositing H2A.Z at thousands of non-canonical sites not directly linked to NDRs or histone acetylation. To understand the targeting mechanism of H2A.Z, we presented SWR to a library of canonical nucleosomes isolated from yeast and analyzed the preferred substrates. Our results revealed that SWR preferentially deposited H2A.Z into a subset of endogenous H2A.Z sites, which are overrepresented by polyadenine tracts on the top strands of the DNA duplex at the nucleosomal entry-exit sites. Insertion of polyadenine sequences into recombinant nucleosomes near the outgoing H2A-H2B dimer enhanced SWR's affinity for the nucleosomal substrate and increased its H2A.Z insertion activity. These findings suggest that the genome encodes sequence-based information that facilitates remodeler-mediated targeting of H2A.Z.","journal":"PLoS Biology","year":2025,"id":550587,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":487797,"name":"Leonidas Pierrakeas","orcid":null,"position":1,"is_corresponding":false},{"id":1179604,"name":"Lirong Chan","orcid":null,"position":2,"is_corresponding":false},{"id":1179605,"name":"Shalvi Chowdhury","orcid":null,"position":3,"is_corresponding":false},{"id":1446169,"name":"Emily de Onis","orcid":null,"position":4,"is_corresponding":false},{"id":318949,"name":"Vyacheslav I. Kuznetsov","orcid":null,"position":5,"is_corresponding":false},{"id":281307,"name":"John M. Denu","orcid":"0000-0001-9415-0365","position":6,"is_corresponding":false},{"id":294291,"name":"Ed Luk","orcid":"0000-0002-6619-2258","position":7,"is_corresponding":false},{"id":1179603,"name":"Cynthia Converso","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:54:16.596730Z","pmid":"40354500","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":[]}