{"doi":"10.1016/j.celrep.2020.01.108","title":"Dissecting the Regulatory Strategies of NF-κB RelA Target Genes in the Inflammatory Response Reveals Differential Transactivation Logics","abstract":"Nuclear factor κB (NF-κB) RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (chromatin immunoprecipitation sequencing [ChIP-seq]) and functional (RNA sequencing [RNA-seq] in knockouts) datasets. We then dissected each gene's regulatory strategy by testing RelA variants in a primary-cell genetic-complementation assay. All endogenous target genes require RelA to make DNA-base-specific contacts, and none are activatable by the DNA binding domain alone. However, endogenous target genes differ widely in how they employ the two transactivation domains. Through model-aided analysis of the dynamic time-course data, we reveal the gene-specific synergy and redundancy of TA1 and TA2. Given that post-translational modifications control TA1 activity and intrinsic affinity for coactivators determines TA2 activity, the differential TA logics suggests context-dependent versus context-independent control of endogenous RelA-target genes. Although some inflammatory initiators appear to require co-stimulatory TA1 activation, inflammatory resolvers are a part of the NF-κB RelA core response.","journal":"Cell Reports","year":2020,"id":58071,"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":74,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":304196,"name":"Kensei Kishimoto","orcid":"0000-0002-0745-1969","position":1,"is_corresponding":false},{"id":304197,"name":"Jeremy Davis‐Turak","orcid":"0000-0002-4462-5171","position":2,"is_corresponding":false},{"id":304198,"name":"Aditya Pimplaskar","orcid":"0000-0002-5660-7210","position":3,"is_corresponding":false},{"id":304199,"name":"Cheng Zhang","orcid":"0000-0003-3863-2866","position":4,"is_corresponding":false},{"id":217931,"name":"Roberto Spreafico","orcid":"0000-0001-8282-7658","position":5,"is_corresponding":false},{"id":304200,"name":"Emily Y. Chen","orcid":"0000-0002-5340-3175","position":6,"is_corresponding":false},{"id":304201,"name":"Amy Tam","orcid":"0000-0003-2072-3436","position":7,"is_corresponding":false},{"id":304202,"name":"Gourisankar Ghosh","orcid":"0000-0001-6311-7351","position":8,"is_corresponding":false},{"id":304203,"name":"Simon Mitchell","orcid":"0000-0003-1091-6349","position":9,"is_corresponding":false},{"id":304204,"name":"Alexander Hoffmann","orcid":"0000-0002-5607-3845","position":10,"is_corresponding":false},{"id":306321,"name":"Kim A. Ngo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T21:07:11.345501Z","pmid":"32101750","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":[]}