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 journalArticle

8 Citations (Scopus)

Abstract

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/EBPbeta and YY1. In wild-type BMMCs, C/EBPbeta expression predominates over YY1 expression, and thus C/EBPbeta 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/EBPbeta. Hypertranscription of the mMCP-2 gene in IL-15-deficient BMMCs is 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.

Original languageEnglish
Pages (from-to)32635-41
Number of pages7
JournalJournal of Biological Chemistry
Volume284
Issue number47
DOIs
Publication statusPublished - Nov 20 2009

Fingerprint

Interleukin-15
Mast Cells
CCAAT-Enhancer-Binding Protein-beta
Bone
Bone Marrow
Peptide Hydrolases
Methylation
Transcription
Cytokines
YY1 Transcription Factor
Acetylation
Biogenic Amines
Adaptive Immunity
Chemokines
Innate Immunity
Gene expression
Histones
chymase 2
Transcription Factors
Genes

Keywords

  • Animals
  • Base Sequence
  • Bone Marrow Cells
  • CCAAT-Enhancer-Binding Protein-beta
  • COS Cells
  • Cercopithecus aethiops
  • Chymases
  • Epigenesis, Genetic
  • Histones
  • Humans
  • Interleukin-15
  • Mast Cells
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Transcription, Genetic
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Mirghomizadeh, F., Bullwinkel, J., Orinska, Z., Janssen, O., Petersen, A., Singh, P. B., & Bulfone-Paus, S. (2009). Transcriptional regulation of mouse mast cell protease-2 by interleukin-15. Journal of Biological Chemistry, 284(47), 32635-41. https://doi.org/10.1074/jbc.M109.015446

Transcriptional regulation of mouse mast cell protease-2 by interleukin-15. / Mirghomizadeh, Farhad; Bullwinkel, Jörn; Orinska, Zane; Janssen, Ottmar; Petersen, Arnd; Singh, Prim B; Bulfone-Paus, Silvia.

In: Journal of Biological Chemistry, Vol. 284, No. 47, 20.11.2009, p. 32635-41.

Research output: Contribution to journalArticle

Mirghomizadeh, F, Bullwinkel, J, Orinska, Z, Janssen, O, Petersen, A, Singh, PB & Bulfone-Paus, S 2009, 'Transcriptional regulation of mouse mast cell protease-2 by interleukin-15', Journal of Biological Chemistry, vol. 284, no. 47, pp. 32635-41. https://doi.org/10.1074/jbc.M109.015446
Mirghomizadeh F, Bullwinkel J, Orinska Z, Janssen O, Petersen A, Singh PB et al. Transcriptional regulation of mouse mast cell protease-2 by interleukin-15. Journal of Biological Chemistry. 2009 Nov 20;284(47):32635-41. https://doi.org/10.1074/jbc.M109.015446
Mirghomizadeh, Farhad ; Bullwinkel, Jörn ; Orinska, Zane ; Janssen, Ottmar ; Petersen, Arnd ; Singh, Prim B ; Bulfone-Paus, Silvia. / Transcriptional regulation of mouse mast cell protease-2 by interleukin-15. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 47. pp. 32635-41.
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AB - 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/EBPbeta and YY1. In wild-type BMMCs, C/EBPbeta expression predominates over YY1 expression, and thus C/EBPbeta 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/EBPbeta. Hypertranscription of the mMCP-2 gene in IL-15-deficient BMMCs is 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.

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KW - Base Sequence

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