Cooperative Transcriptional Activation of Antimicrobial Genes by STAT and NF-κB Pathways by Concerted Recruitment of the Mediator Complex

Sebastian Wienerroither, Priyank Shukla, Matthias Farlik, Andrea Majoros, Bernadette Stych, Claus Vogl, HyeonJoo Cheon, George R Stark, Birgit Strobl, Mathias Mueller, Thomas Decker

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    19 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)300-312
    Number of pages13
    JournalCell Reports
    Volume12
    Issue number2
    Early online date2 Jul 2015
    DOIs
    Publication statusPublished - 14 Jul 2015

    Keywords

    • Jak-Stat Signalling
    • NF-kB
    • ChIP-Seq

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    Cite this

    Wienerroither, S., Shukla, P., Farlik, M., Majoros, A., Stych, B., Vogl, C., Cheon, H., Stark, G. R., Strobl, B., Mueller, M., & Decker, T. (2015). Cooperative Transcriptional Activation of Antimicrobial Genes by STAT and NF-κB Pathways by Concerted Recruitment of the Mediator Complex. Cell Reports, 12(2), 300-312. https://doi.org/10.1016/j.celrep.2015.06.021