Interleukin-15 induces IL-12 receptor β1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling

Tipayaratn Musikacharoen, Asako Oguma, Yasunobu Yoshikai, Norika Chiba, Akio Masuda, Tetsuya Matsuguchi

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Interleukin-12 receptor β1 (IL12RB1) is expressed on a variety of immune cells, including T and natural killer (NK) cells and macrophages, and is involved in innate and adaptive immune responses. Levels of IL12RB1 mRNA are dynamically regulated by various cytokines, including interferon-γ (IFN-γ) and IL-15. To reveal the regulatory mechanisms governing IL12RB1 gene expression, we analyzed the transcriptional regulatory region of the mouse IL12RB1 gene. Promoter analyses in a mouse macrophage cell line, RAW264.7, revealed that the 2508-bp region upstream of the transcriptional start Site is sufficient for the full transcriptional activation of the IL12RB1 gene by IFN-γ or IL-15. Analyses of the deletion mutants revealed critical roles of IRE/ISRE and ETS/PU.1 elements, to which IRF3 and PU.1, respectively, bound. Notably, chromatin immunoprecipitation (ChIP) assays revealed IL-15 rapidly induced histone H3 acetylation at the IL12RB1 promoter. Consistently, IL-15, as a histone deacetylase inhibitor, synergistically enhanced IL12RB1 gene expression and promoter activation by IFN-γ through increased protein binding to ETS/PU.1 and IRE/ISRE sites. Additionally, IL12RB1 promoter activation by IFN-γ was enhanced by the coexpression of a coactivator protein, CBP. Thus, IL-15 induces chromatin remodeling of the IL12RB1 gene promoter, increasing IL12RB1 mRNA expression in synergy with IFN-γ through the recruitment of PU.1 and IRF3.

    Original languageEnglish
    Pages (from-to)711-720
    Number of pages10
    JournalBlood
    Volume105
    Issue number2
    DOIs
    Publication statusPublished - Jan 15 2005

    Fingerprint

    Interleukin-12 Receptors
    Interleukin-15
    Chromatin Assembly and Disassembly
    Gene expression
    Interferons
    Chromatin
    Gene Expression
    Genes
    Macrophages
    Chemical activation
    Acetylation
    Messenger RNA
    Natural Killer T-Cells
    Histone Deacetylase Inhibitors
    Chromatin Immunoprecipitation
    Nucleic Acid Regulatory Sequences
    Adaptive Immunity
    Innate Immunity
    Protein Binding
    Histones

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

    Cite this

    Musikacharoen, T., Oguma, A., Yoshikai, Y., Chiba, N., Masuda, A., & Matsuguchi, T. (2005). Interleukin-15 induces IL-12 receptor β1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. Blood, 105(2), 711-720. https://doi.org/10.1182/blood-2004-03-0842

    Interleukin-15 induces IL-12 receptor β1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. / Musikacharoen, Tipayaratn; Oguma, Asako; Yoshikai, Yasunobu; Chiba, Norika; Masuda, Akio; Matsuguchi, Tetsuya.

    In: Blood, Vol. 105, No. 2, 15.01.2005, p. 711-720.

    Research output: Contribution to journalArticle

    Musikacharoen, T, Oguma, A, Yoshikai, Y, Chiba, N, Masuda, A & Matsuguchi, T 2005, 'Interleukin-15 induces IL-12 receptor β1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling', Blood, vol. 105, no. 2, pp. 711-720. https://doi.org/10.1182/blood-2004-03-0842
    Musikacharoen, Tipayaratn ; Oguma, Asako ; Yoshikai, Yasunobu ; Chiba, Norika ; Masuda, Akio ; Matsuguchi, Tetsuya. / Interleukin-15 induces IL-12 receptor β1 gene expression through PU.1 and IRF 3 by targeting chromatin remodeling. In: Blood. 2005 ; Vol. 105, No. 2. pp. 711-720.
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