{"doi":"10.1016/j.jbc.2025.110859","title":"Jade1 and the HBO1 histone acetyltransferase complex are spatial-selective cofactors of the pluripotency transcription factor Oct4","abstract":"Oct4 is a master regulator of pluripotency. Potential Oct4 interactors have been cataloged but the manner and significance of these interactions are incompletely defined. Oct4 is capable of binding to DNA in multiple configurations, however the relationship between these configurations and cofactor recruitment (and hence transcription output) are unknown. Here, we show that Oct4 interacts with common and unique proteins when bound to DNA in different configurations. A unique protein is Jade1, a component of HBO histone acetyltransferase complexes. Jade1 preferentially associates with Oct4 when bound to more palindromic Octamer-Related Element (MORE) DNA sequences that bind Oct4 dimers. Surprisingly, we find that the Oct4 N-terminal activation domain, rather than facilitating Jade1 binding, serves as an autoinhibitory domain that dampens the interaction. Chromatin immunoprecipitation and sequencing using HBO1, the enzymatic component of the complex, identifies a preference for binding adjacent to Oct4 at MORE sites. Using purified recombinant proteins and nucleosome complexes, we show that the HBO1 complex acetylates histone H3K9 within nucleosomes more efficiently when Oct4 is cobound to a MORE. An Oct4 mutant with superior MORE binding characteristics also shows superior ability to catalyze H3K9 acetylation. Jade1 knockdown reduces H3K9Ac at regions where Oct4 binds a MORE but not a simple octamer. Cryo-electron microscopy reveals that Oct4 bound to a MORE near the nucleosome entry/exit site partially unwinds DNA from nucleosome core particles, and identifies additional mass associated with the HBO1 complex. These results identify a novel mechanism of transcriptional regulation by Oct4.","journal":"Journal of Biological Chemistry","year":2025,"id":547965,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE279191"]},"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":1031041,"name":"Asit Manna","orcid":"0000-0003-0922-9381","position":1,"is_corresponding":false},{"id":328012,"name":"Li Li","orcid":"0000-0003-2342-3658","position":2,"is_corresponding":false},{"id":80262,"name":"Zuolian Shen","orcid":null,"position":3,"is_corresponding":false},{"id":401474,"name":"Hiroshi Handa","orcid":"0000-0001-6656-9521","position":4,"is_corresponding":false},{"id":196192,"name":"Mahesh B. Chandrasekharan","orcid":"0000-0002-9956-8354","position":5,"is_corresponding":false},{"id":15427,"name":"Dean Tantin","orcid":"0000-0003-1354-8385","position":6,"is_corresponding":false},{"id":331856,"name":"Yifan Wu","orcid":"0000-0001-6345-4219","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:53:53.962932Z","pmid":"41489900","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":[]}