{"doi":"10.1101/2023.11.08.566246","title":"Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1","abstract":"Abstract Despite the unique ability of pioneer transcription factors (PFs) to target nucleosomal sites in closed chromatin, they only bind a small fraction of their genomic motifs. The underlying mechanism of this selectivity is not well understood. Here, we design a high-throughput assay called ChIP-ISO to systematically dissect sequence features affecting the binding specificity of a classic PF, FOXA1. Combining ChIP-ISO with in vitro and neural network analyses, we find that 1) FOXA1 binding is strongly affected by co-binding TFs AP-1 and CEBPB, 2) FOXA1 and AP-1 show binding cooperativity in vitro , 3) FOXA1’s binding is determined more by local sequences than chromatin context, including eu-/heterochromatin, and 4) AP-1 is partially responsible for differential binding of FOXA1 in different cell types. Our study presents a framework for elucidating genetic rules underlying PF binding specificity and reveals a mechanism for context-specific regulation of its binding.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393820,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"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":1157001,"name":"Holly Kleinschmidt","orcid":null,"position":1,"is_corresponding":false},{"id":71761,"name":"Jianyu Yang","orcid":"0000-0002-0195-4100","position":2,"is_corresponding":false},{"id":832256,"name":"Erik M. Leith","orcid":"0000-0003-2883-7753","position":3,"is_corresponding":false},{"id":1168318,"name":"Jenna K. Johnson","orcid":null,"position":4,"is_corresponding":false},{"id":274210,"name":"Song Tan","orcid":"0000-0002-6698-8475","position":5,"is_corresponding":false},{"id":4943,"name":"Shaun Mahony","orcid":"0000-0002-2641-1807","position":6,"is_corresponding":false},{"id":447230,"name":"Lu Bai","orcid":"0000-0003-3667-2944","position":7,"is_corresponding":false},{"id":1156644,"name":"Cheng Xu","orcid":"0000-0002-4503-6029","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:05.913428Z","pmid":"37986839","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":[]}