{"doi":"10.1016/j.molcel.2023.12.004","title":"p300 is an obligate integrator of combinatorial transcription factor inputs","abstract":"Transcription coactivators are proteins or protein complexes that mediate transcription factor (TF) function. However, they lack DNA-binding capacity, prompting the question of how they engage target loci. Three non-exclusive hypotheses have been posited: coactivators are recruited by complexing with TFs, by binding histones through epigenetic reader domains, or by partitioning into condensates through their extensive intrinsically disordered regions. Using p300 as a prototypical coactivator, we systematically mutated its annotated domains and show by single-molecule tracking in live U2OS cells that coactivator-chromatin binding depends entirely on combinatorial binding of multiple TF-interaction domains. Furthermore, we demonstrate that acetyltransferase activity opposes p300-chromatin association and that the N-terminal TF-interaction domains regulate that activity. Single TF-interaction domains are insufficient for chromatin binding and regulation of catalytic activity, implying a principle that we speculate could broadly apply to eukaryotic gene regulation: a TF must act in coordination with other TFs to recruit coactivator activity.","journal":"Molecular Cell","year":2023,"id":319831,"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":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":804589,"name":"Jonathan P. Karr","orcid":null,"position":1,"is_corresponding":false},{"id":554005,"name":"Thomas G.W. Graham","orcid":"0000-0001-5189-4313","position":2,"is_corresponding":false},{"id":649431,"name":"Gina M. Dailey","orcid":"0000-0002-8988-963X","position":3,"is_corresponding":false},{"id":868598,"name":"Gloria Zhang","orcid":"0000-0001-9064-3488","position":4,"is_corresponding":false},{"id":109375,"name":"Robert Tjian","orcid":"0000-0003-0539-8217","position":5,"is_corresponding":false},{"id":109376,"name":"Xavier Darzacq","orcid":"0000-0003-2537-8395","position":6,"is_corresponding":false},{"id":323326,"name":"John J. Ferrie","orcid":"0000-0001-7934-7266","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:07:17.361058Z","pmid":"38159566","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":[]}