Nonconventional Initiation Complex Assembly by STAT and NF-κB Transcription Factors Regulates Nitric Oxide Synthase Expression
Copyright policy )Nonconventional Initiation Complex Assembly by STAT and NF-κB Transcription Factors Regulates Nitric Oxide Synthase Expression
Transcriptional regulation of the Nos2 gene encoding inducible nitric oxide synthase (iNOS) requires type I interferon (IFN-I) signaling and additional signals emanating from pattern recognition receptors. Here we showed sequential and cooperative contributions of the transcription factors ISGF3 (a complex containing STAT1, STAT2, and IRF9 subunits) and NF-kappaB to the transcriptional induction of the Nos2 gene in macrophages infected with the intracellular bacterial pathogen Listeria monocytogenes. NF-kappaB preceded ISGF3 at the Nos2 promoter and generated a transcriptional memory effect by depositing basal transcription factor TFIIH with the associated CDK7 kinase for serine 5 phosphorylation of the RNA polymerase II (pol II) carboxyterminal domain (CTD). Subsequent to TFIIH deposition by NF-kappaB, ISGF3 attracted the pol II enzyme and phosphorylation at CTD S5 occurred. Thus, STATs and NF-kappaB cooperate through pol II promoter recruitment and the phosphorylation of its CTD, respectively, as a prerequisite for productive elongation of iNOS mRNA.
- Columbia University United States
- King’s University United States
- Rechts der Isar Hospital Germany
- Columbia University
- Universität Wien Austria
Immunology, Nitric Oxide Synthase Type II, Article, Gene Expression Regulation, Enzymologic, Mice, Immunology and Allergy, Animals, Listeriosis, 106001 Allgemeine Biologie, MOLIMMUNO, Cells, Cultured, Mice, Knockout, Macrophages, NF-kappa B, Interferon-Stimulated Gene Factor 3, Listeria monocytogenes, Cyclin-Dependent Kinases, 106001 General biology, Mice, Inbred C57BL, STAT Transcription Factors, Infectious Diseases, SIGNALING, Interferon Type I, RNA, RNA Polymerase II, Transcription Factor TFIIH, Cyclin-Dependent Kinase-Activating Kinase, Protein Binding
Immunology, Nitric Oxide Synthase Type II, Article, Gene Expression Regulation, Enzymologic, Mice, Immunology and Allergy, Animals, Listeriosis, 106001 Allgemeine Biologie, MOLIMMUNO, Cells, Cultured, Mice, Knockout, Macrophages, NF-kappa B, Interferon-Stimulated Gene Factor 3, Listeria monocytogenes, Cyclin-Dependent Kinases, 106001 General biology, Mice, Inbred C57BL, STAT Transcription Factors, Infectious Diseases, SIGNALING, Interferon Type I, RNA, RNA Polymerase II, Transcription Factor TFIIH, Cyclin-Dependent Kinase-Activating Kinase, Protein Binding
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