{"doi":"10.7554/elife.105915","title":"Genome organization by SATB1 binding to base-unpairing regions (BURs) provides a scaffold for SATB1-regulated gene expression","abstract":"Mammalian genomes are organized by multi-level folding; yet how this organization contributes to cell-type-specific transcription remains unclear. SATB1 forms a nuclear substructure that resists high-salt extraction. SATB1 binds base-unpairing regions (BURs), genomic elements with high unwinding propensities. In mouse thymocytes, we found that SATB1 establishes a two-tiered chromatin organization: one through indirect binding to transcriptionally active DNase 1-accessible chromatin and another by direct binding to BURs in the DNase 1-inaccessible nuclear substructure. Recently published ChIP-seq datasets show SATB1 binding to accessible chromatin at enhancers and CTCF sites, but not to BURs. By employing urea ChIP-seq, which retains only directly bound protein:DNA complexes, we found that BURs, but not CTCF sites, are direct SATB1 binding targets genome-wide. BURs bound to the SATB1 nuclear substructure interact with accessible chromatin, crossing multiple topologically associated domains (TADs). SATB1 is required for these megabase-scale interactions linked to cell-type-specific gene expression. BURs are highly enriched within transcriptionally repressive lamina-associated domains (LADs). Besides these BURs, SATB1 anchors some BURs (18%) outside LADs near genes in otherwise accessible chromatin to the SATB1 nuclear substructure. Only a subset of total BURs is bound to SATB1, depending on cell type. Notably, despite the mutually exclusive SATB1-binding profiles uncovered by the two ChIP-seq methods, we found most peaks in both profiles are valid and require SATB1. Based on these and previous data, we propose that the SATB1 protein network forms a chromatin scaffold, providing an interface that connects accessible chromatin to a subnuclear architectural structure, thereby facilitating the three-dimensional organization linked to cell-type-specific gene expression.","journal":"eLife","year":2025,"id":555454,"datarank":0.22164590076044766,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.013701746592464033,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.013701746592464033,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE191146","GSE173476","GSE18776"],"SRA":["DRP003376"]},"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":561716,"name":"Xianrong Wong","orcid":"0000-0002-1995-7043","position":1,"is_corresponding":false},{"id":1454233,"name":"Mari Grange","orcid":null,"position":2,"is_corresponding":false},{"id":983185,"name":"Tom Sexton","orcid":"0000-0002-7824-1846","position":3,"is_corresponding":false},{"id":1146635,"name":"Hunter W. Richards","orcid":"0000-0001-9913-089X","position":4,"is_corresponding":false},{"id":1453743,"name":"Yohko Kitagawa","orcid":"0000-0002-3954-6807","position":5,"is_corresponding":false},{"id":36102,"name":"Shimon Sakaguchi","orcid":"0000-0001-8265-6094","position":6,"is_corresponding":false},{"id":486152,"name":"Ya‐Chen Liang","orcid":"0000-0001-7813-8921","position":7,"is_corresponding":false},{"id":454746,"name":"Cheng‐Ming Chuong","orcid":"0000-0001-9673-3994","position":8,"is_corresponding":false},{"id":1106725,"name":"Vladimir A. Botchkarev","orcid":"0000-0002-5212-5353","position":9,"is_corresponding":false},{"id":118806,"name":"Ichiro Taniuchi","orcid":"0000-0002-9853-9068","position":10,"is_corresponding":false},{"id":561718,"name":"Karen Reddy","orcid":"0000-0003-4548-5999","position":11,"is_corresponding":false},{"id":783458,"name":"Terumi Kohwi-shigematsu","orcid":"0000-0002-5988-0669","position":12,"is_corresponding":false},{"id":833055,"name":"Yoshinori Kohwi","orcid":"0000-0002-5443-0909","position":0,"is_corresponding":true}],"reference_count":144,"raw_metadata":null,"created_at":"2026-07-19T02:54:59.329539Z","pmid":"41036778","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":[]}