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

Farhad Mirghomizadeh1, Jörn Bullwinkel, Zane Orinska

  • 1Division of Immunobiology, Department of Immunology and Cell Biology, Research Center Borstel, 23845 Borstel, Germany.

The Journal of Biological Chemistry
|October 6, 2009
PubMed

Insights

Interleukin-15 (IL-15) regulates mast cell protease-2 (mMCP-2) gene transcription by controlling transcription factors C/EBPbeta and YY1. This cytokine-mediated regulation involves epigenetic mechanisms like non-CpG methylation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • Mast cells (MCs) are crucial immune cells releasing various mediators.
  • Interleukin-15 (IL-15) was previously identified as a regulator of mast cell protease activity.
  • Mouse mast cell protease-2 (mMCP-2) is a key protease regulated by IL-15.

Purpose of the Study:

  • To elucidate the mechanism by which IL-15 regulates mMCP-2 transcription.
  • To investigate the role of transcription factors C/EBPbeta and YY1 in IL-15-mediated mMCP-2 regulation.
  • To explore the epigenetic modifications involved in mMCP-2 gene expression control.

Main Methods:

  • Analysis of wild-type and IL-15-deficient bone marrow-derived mast cells (BMMCs).
  • Assessment of C/EBPbeta and YY1 expression and promoter binding.
  • Chromatin analysis including histone acetylation and non-CpG methylation.

Main Results:

  • IL-15 inhibits mMCP-2 transcription in BMMCs by differentially regulating C/EBPbeta and YY1.
  • C/EBPbeta predominates in wild-type BMMCs, while YY1 dominates in IL-15-deficient BMMCs, affecting mMCP-2 promoter binding.
  • Hypertranscription of mMCP-2 in IL-15-deficient BMMCs correlates with histone acetylation and non-CpG methylation.

Conclusions:

  • IL-15 controls mMCP-2 transcription via C/EBPbeta and YY1 balance.
  • Non-CpG methylation is implicated in maintaining an open chromatin state for protease gene expression.
  • This study proposes a novel model for cytokine-controlled protease gene transcription involving epigenetic regulation.

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