{"doi":"10.1101/gr.280357.124","title":"Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-kB binding","abstract":"Transposable elements (TEs) provide a source of transcription factor (TF) binding sites that can rewire gene regulatory networks. NF-kB is an evolutionarily conserved TF complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we perform a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF-stimulated primary aortic endothelial cells isolated from human, mouse, and cow, we find that 55 TE subfamilies are associated with RELA-bound regions, many of which reside near TNF-responsive genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 RELA-bound regions in cow. By comparing RELA binding data across species, we also find several examples of RELA motif-bearing TEs that colonized the genome prior to the divergence of the three species and contributed to species-specific RELA binding. For example, we find human RELA-bound MER81 instances are enriched for the interferon gamma pathway and demonstrate that one RELA-bound MER81 element can control the TNF-induced expression of interferon gamma receptor 2 ( IFNGR2 ). Using ancestral reconstructions, we find that RELA containing MER81 instances rapidly decayed during early primate evolution (>50 million years ago [MYA]) before stabilizing since the separation of Old World monkeys (<50 MYA). Taken together, our results suggest ancient and lineage-specific transposon subfamilies contributed to mammalian NF-kB regulatory networks.","journal":"Genome Research","year":2025,"id":555216,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9435,"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":983778,"name":"Tiegh Taylor","orcid":null,"position":1,"is_corresponding":false},{"id":713018,"name":"Kumaragurubaran Rathnakumar","orcid":"0000-0002-9932-3357","position":2,"is_corresponding":false},{"id":713015,"name":"Nadiya Khyzha","orcid":"0000-0001-8804-0039","position":3,"is_corresponding":false},{"id":713017,"name":"Minggao Liang","orcid":"0000-0002-4451-0921","position":4,"is_corresponding":false},{"id":713014,"name":"Azad Alizada","orcid":"0000-0002-2313-965X","position":5,"is_corresponding":false},{"id":853886,"name":"Laura F. Campitelli","orcid":null,"position":6,"is_corresponding":false},{"id":885575,"name":"Sara E. Pour","orcid":"0009-0009-6201-1921","position":7,"is_corresponding":false},{"id":998077,"name":"Zain M. Patel","orcid":null,"position":8,"is_corresponding":false},{"id":713016,"name":"Lina Antounians","orcid":"0000-0002-8307-3306","position":9,"is_corresponding":false},{"id":983182,"name":"Ian C. Tobias","orcid":"0000-0003-4901-9856","position":10,"is_corresponding":false},{"id":581102,"name":"Huayun Hou","orcid":"0000-0003-3971-1427","position":11,"is_corresponding":false},{"id":43029,"name":"Timothy R. Hughes","orcid":"0000-0002-8721-4719","position":12,"is_corresponding":false},{"id":29482,"name":"Sushmita Roy","orcid":"0000-0002-3694-1705","position":13,"is_corresponding":false},{"id":983184,"name":"Jennifer A. Mitchell","orcid":"0000-0002-7147-4604","position":14,"is_corresponding":false},{"id":713020,"name":"Jason E. Fish","orcid":"0000-0003-0640-7277","position":15,"is_corresponding":false},{"id":79291,"name":"Michael D. Wilson","orcid":"0000-0002-4015-3066","position":16,"is_corresponding":false},{"id":713651,"name":"Liangxi Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:54:59.329539Z","pmid":"40480832","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":[]}