{"doi":"10.1101/2025.10.01.679912","title":"Acidic transcription factors position the genome at nuclear speckles through transcription dependent and independent mechanisms","abstract":"A small fraction of the genome positions reproducibly near nuclear speckles (NS), increasing expression and/or splicing efficiency of NS-associated genes. How specific genomic regions target to NS remains unclear. Here, we demonstrate that establishment of genome-wide NS-association occurs independent of active transcription. We show that DNA sequences derived from NS-associated regions integrated as transgenes autonomously target to NS. By systematically dissecting one such genomic locus, the COL1A1-SGCA locus, we identified redundant NS-targeting cis regulatory elements, including a ∼600 bp fragment with 17 binding motifs for 8 transcription factors (TFs). Four NS-targeting TFs within this fragment contain acidic activation domains (AADs) that provide both chromatin-context and transcription-dependent NS-targeting, a property that appears common among several other tested AADs. A subset of acidic activator TFs contain an additional, transcription-independent NS-targeting activity. Our findings establish diverse and partially redundant NS-targeting activities, which may facilitate dynamic gene positioning at NS periphery for context-specific transcriptional responses.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559206,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"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":1460421,"name":"Purnam Ghosh","orcid":"0000-0003-0442-2764","position":1,"is_corresponding":false},{"id":550185,"name":"Liguo Zhang","orcid":"0000-0001-7346-8964","position":2,"is_corresponding":false},{"id":566225,"name":"Meng Zhang","orcid":"0000-0002-4076-6276","position":3,"is_corresponding":false},{"id":263533,"name":"Huimin Zhao","orcid":"0000-0002-9069-6739","position":4,"is_corresponding":false},{"id":289200,"name":"Andrew S. Belmont","orcid":"0000-0002-6540-0801","position":5,"is_corresponding":false},{"id":1460420,"name":"Pankaj Chaturvedi","orcid":"0000-0001-7596-2165","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41256630","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":[]}