Transcriptional regulation of mouse mast cell protease-2 by interleukin-15

Farhad Mirghomizadeh, Jörn Bullwinkel, Zane Orinska, Ottmar Janssen, Arnd Petersen, Prim B. Singh, Silvia Bulfone-Paus

    Research output: Contribution to journalArticlepeer-review


    Mast cells (MCs) play a critical role in innate and adaptive immunity through the release of cytokines, chemokines, lipid mediators, biogenic amines, and proteases. We recently showed that the activities of MC proteases are transcriptionally regulated by intracellularly retained interleukin-15 (IL-15), and we provided evidence that this cytokine acts as a specific regulator of mouse mast cell protease-2 (mMCP-2). Here, we show that in wild-type bone marrow-derived mast cells (BMMCs) IL-15 inhibits mMCP-2 transcription indirectly by inducing differential expression and mMCP-2 promoter binding of the bifunctional transcription factors C/EBPβ and YY1. In wild-type BMMCs, C/EBPβ expression predominates over YY1 expression, and thus C/EBPβ preferentially binds to the mMCP-2 promoter. In IL-15-deficient BMMCs, the opposite is found: YY1 expression predominates and binds to the mMCP-2 promoter at the expense of C/EBPβ. Hypertranscription of the mMCP-2 gene in IL-15-deficient BMMC sis associated with histone acetylation and, intriguingly, with methylation of non-CpG dinucleotides within the MCP-2 promoter. This suggests a novel model of cytokine-controlled protease transcription: non-CpG methylation maintains a chromosomal domain in an "open" configuration that is permissive for gene expression. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.
    Original languageEnglish
    Pages (from-to)32635-32641
    Number of pages6
    JournalJournal of Biological Chemistry
    Issue number47
    Publication statusPublished - 20 Nov 2009


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