{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:09:43Z","timestamp":1790878183309,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Molecular Biology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  NF-\u03baB must remain bound to chromatin long enough to activate innate immune genes, but what stabilizes this transcriptionally productive state is unknown. Here, we identify the Integrator complex as an essential determinant of NF-\u03baB chromatin residence in mouse and human cells. Integrator associated with NF-\u03baB and co-occupied its genomic targets. Single-molecule tracking revealed that Integrator markedly prolonged the chromatin residence of RELA molecules in a low-mobility state. Catalytically inactive INTS11-E203Q fully restored NF-\u03baB\u2013dependent transcription, separating this chromatin-retention function from RNA cleavage. Conditional\n                  <jats:italic>Ints11<\/jats:italic>\n                  deletion abolished TLR4-dependent dendritic-cell activation in adult mice and impaired LPS-induced transcription in mouse embryonic fibroblasts. Loss of Integrator in human cancer cells similarly suppressed TNF\u03b1-induced inflammatory gene expression. These findings uncover a noncatalytic function for Integrator that stabilizes NF-\u03baB at enhancers, complementing its established catalytic control of RNA polymerase II pause release. By coupling signal recognition at enhancers to productive elongation, Integrator provides a molecular solution to a central challenge of multicellularity: converting transient extracellular cues into coherent gene-expression programs across complex chromatin landscapes.\n                <\/jats:p>","DOI":"10.64898\/2026.09.25.754463","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:40:33Z","timestamp":1790606433000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrator governs NF-\u03baB dwell time on chromatin to drive inflammatory transcription"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-9725","authenticated-orcid":false,"given":"Pradeep Kumar Reddy","family":"Cingaram","sequence":"first","affiliation":[{"name":"Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10 Avenue, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyin","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10 Avenue, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1600, NW 10 Ave, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Gomes Dos Santos","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10 Avenue, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel S.","family":"Gaidosh","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10 Avenue, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Sidoli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Albert Einstein College of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biophysics, Siteman Cancer Center, Washington University in St. Louis School of Medicine, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Lai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Conservation and Utilization of Bio-Resources in Yunnan and Center for Life Science, School of Life Sciences, Yunnan University, Kunming, 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, the University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, 1501 NW 10 Avenue, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Miura","family":"Lavezzo","sequence":"additional","affiliation":[{"name":"Guilherme Miura Lavezzo Consultoria em tecnologia da informa\u00e7\u00e3o LTDA, Rua Major Sampaio, 65 - 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