{"doi":"10.1101/gad.348431.121","title":"Essential histone chaperones collaborate to regulate transcription and chromatin integrity","abstract":"Histone chaperones are critical for controlling chromatin integrity during transcription, DNA replication, and DNA repair. Three conserved and essential chaperones, Spt6, Spn1/Iws1, and FACT, associate with elongating RNA polymerase II and interact with each other physically and/or functionally; however, there is little understanding of their individual functions or their relationships with each other. In this study, we selected for suppressors of a temperature-sensitive spt6 mutation that disrupts the Spt6-Spn1 physical interaction and that also causes both transcription and chromatin defects. This selection identified novel mutations in FACT. Surprisingly, suppression by FACT did not restore the Spt6-Spn1 interaction, based on coimmunoprecipitation, ChIP, and mass spectrometry experiments. Furthermore, suppression by FACT bypassed the complete loss of Spn1. Interestingly, the FACT suppressor mutations cluster along the FACT-nucleosome interface, suggesting that they alter FACT-nucleosome interactions. In agreement with this observation, we showed that the spt6 mutation that disrupts the Spt6-Spn1 interaction caused an elevated level of FACT association with chromatin, while the FACT suppressors reduced the level of FACT-chromatin association, thereby restoring a normal Spt6-FACT balance on chromatin. Taken together, these studies reveal previously unknown regulation between histone chaperones that is critical for their essential in vivo functions.","journal":"Genes & Development","year":2021,"id":213145,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":489230,"name":"James Chuang","orcid":"0000-0002-9802-1808","position":1,"is_corresponding":false},{"id":108497,"name":"Dhawal Jain","orcid":"0000-0001-9437-7201","position":2,"is_corresponding":false},{"id":489761,"name":"Natalia I. Reim","orcid":null,"position":3,"is_corresponding":false},{"id":574986,"name":"Francheska López-Rivera","orcid":"0000-0002-5160-6120","position":4,"is_corresponding":false},{"id":585462,"name":"Magdalena Murawska","orcid":"0000-0001-8956-7545","position":5,"is_corresponding":false},{"id":586239,"name":"Dan Spatt","orcid":null,"position":6,"is_corresponding":false},{"id":457648,"name":"L. Stirling Churchman","orcid":"0000-0003-3888-2574","position":7,"is_corresponding":false},{"id":1821,"name":"Peter J. Park","orcid":"0000-0001-9378-960X","position":8,"is_corresponding":false},{"id":266475,"name":"Fred Winston","orcid":"0000-0002-4759-5537","position":9,"is_corresponding":false},{"id":585461,"name":"Olga Viktorovskaya","orcid":"0000-0003-0884-1042","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:31.378994Z","pmid":"33888559","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":[]}