title: Cooperative Transcriptional Activation of Antimicrobial Genes by STAT and NF-κB Pathways by Concerted Recruitment of the Mediator Complex.
abstract: The transcriptional response to infection with the bacterium Listeria monocytogenes (Lm) requires cooperative signals of the type I interferon (IFN-I)-stimulated JAK-STAT and proinflammatory NF-κB pathways. Using ChIP-seq analysis, we define genes induced in Lm-infected macrophages through synergistic transcriptional activation by NF-κB and the IFN-I-activated transcription factor ISGF3. Using the Nos2 and IL6 genes as prime examples of this group, we show that NF-κB functions to recruit enzymes that establish histone marks of transcriptionally active genes. In addition, NF-κB regulates transcriptional elongation by employing the mediator kinase module for the recruitment of the pTEFb complex. ISGF3 has a major role in associating the core mediator with the transcription start as a prerequisite for TFIID and RNA polymerase II (Pol II) binding. Our data suggest that the functional cooperation between two major antimicrobial pathways is based on promoter priming by NF-κB and the engagement of the core mediator for Pol II binding by ISGF3.
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Drive Bohr-Gasse 9, 1030 Vienna, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wienerroither
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Priyank
authors.initials: P
authors.lastname: Shukla
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Lazarettgasse 14, 1090 Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Farlik
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Drive Bohr-Gasse 9, 1030 Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Majoros
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Drive Bohr-Gasse 9, 1030 Vienna, Austria.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Stych
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Claus
authors.initials: C
authors.lastname: Vogl
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: HyeonJoo
authors.initials: H
authors.lastname: Cheon
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Stark
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Strobl
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.affiliation: Max F. Perutz Laboratories, University of Vienna, Drive Bohr-Gasse 9, 1030 Vienna, Austria. Electronic address: thomas.decker@univie.ac.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
mesh_terms: D000818:Animals; D001665:Binding Sites; D051548:Histone Acetyltransferases / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D050832:Interferon-Stimulated Gene Factor 3 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008089:Listeria monocytogenes / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D056892:Mediator Complex / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D035362:Transcription Factor TFIID / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D050832:Interferon-Stimulated Gene Factor 3; D015850:Interleukin-6; C105373:MEN1 protein, human; D056892:Mediator Complex; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D050791:STAT Transcription Factors; D035362:Transcription Factor TFIID; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; D012319:RNA Polymerase II