Zeitschriftenaufsatz
|
2015
Cooperative Transcriptional Activation of Antimicrobial Genes by STAT and NF-κB Pathways by Concerted Recruitment of the Mediator Complex
Autor:in
Wienerroither, Sebastian; Shukla, Priyank; Farlik, Matthias; Majoros, Andrea; Stych, Bernadette; Vogl, C.; Cheon, Hyeon Joo; Stark, G.; Strobl, Birgit; Mueller, Mathias; Decker, T.
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
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-kappa B pathways. Using ChIP-seq analysis, we define genes induced in Lm-infected macrophages through synergistic transcriptional activation by NF-kappa B and the IFN-I-activated transcription factor ISGF3. Using the Nos2 and IL6 genes as prime examples of this group, we show that NF-kappa B functions to recruit enzymes that establish histone marks of transcriptionally active genes. In addition, NF-kappa B 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-kappa B and the engagement of the core mediator for Pol II binding by ISGF3.
Schlagwörter
Animals; Binding Sites; Histone Acetyltransferases/metabolism; Histone-Lysine N-Methyltransferase/metabolism; Interferon-Stimulated Gene Factor 3/genetics; Interferon-Stimulated Gene Factor 3/metabolism; Interleukin-6/genetics; Interleukin-6/metabolism; Listeria monocytogenes/physiology; Macrophages/cytology; Macrophages/immunology; Macrophages/metabolism; Mediator Complex/metabolism*; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B/genetics; NF-kappa B/metabolism*; Nitric Oxide Synthase Type II/genetics; Nitric Oxide Synthase Type II/metabolism; Protein Binding; Proto-Oncogene Proteins/antagonists & inhibitors; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; RNA Polymerase II/metabolism; STAT Transcription Factors/metabolism*; Signal Transduction; Transcription Factor TFIID/metabolism; Transcriptional Activation;
Dokumententyp
Originalarbeit
CC Lizenz
CCBYNCND
Open Access Type
Gold
ISSN/eISSN
2211-1247 -
10.1016/j.celrep.2015.06.021
WoS ID
PubMed ID