{"doi":"10.1016/j.celrep.2025.116633","title":"FoxP3 forms a head-to-head dimer in vivo and stabilizes its multimerization on adjacent microsatellites","abstract":"FoxP3, the master regulator of Tregs, employs two DNA-binding modes to recognize diverse DNA sequences. It multimerizes on long TnG repeats (n = 2-5) to bridge DNA segments and stabilize chromatin loops, and it forms head-to-head (H-H) dimers on inverted repeat forkhead motifs (IR-FKHM) without bridging DNA. Although genomic data confirm its multimeric role, in vivo evidence for H-H dimerization has been elusive. Here, unbiased pull-down sequencing uncovers a range of relaxed motifs that drive H-H dimerization, enabling systematic genome-wide analysis. We demonstrate that FoxP3 binds genomic DNA as both H-H dimers and multimers in Tregs, with H-H binding often seeding and stabilizing multimerization on adjacent TnG repeats-especially on shorter, suboptimal repeats. While multimerization is conserved across FoxP family members, H-H dimerization is unique to FoxP3 orthologs, conferred by its divergent accessory loop. This dual-mode strategy broadens FoxP3's sequence repertoire and enhances its architectural function in chromatin looping.","journal":"Cell Reports","year":2025,"id":535555,"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":0.949,"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":1419177,"name":"Ryan Clark","orcid":"0000-0002-4355-5351","position":1,"is_corresponding":false},{"id":999922,"name":"Wenxiang Zhang","orcid":"0000-0001-6528-7629","position":2,"is_corresponding":false},{"id":305614,"name":"Thibault Viennet","orcid":"0000-0001-5349-0179","position":3,"is_corresponding":false},{"id":1419636,"name":"Cuidie Wang","orcid":null,"position":4,"is_corresponding":false},{"id":218700,"name":"Haribabu Arthanari","orcid":"0000-0002-7281-1289","position":5,"is_corresponding":false},{"id":1369115,"name":"Xi Wang","orcid":"0000-0001-5173-2234","position":6,"is_corresponding":false},{"id":274412,"name":"Sun Hur","orcid":"0000-0001-5005-5550","position":7,"is_corresponding":false},{"id":999921,"name":"Fangwei Leng","orcid":"0000-0001-8027-9387","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41313681","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":[]}