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Eomesodermin promotes interferon-γ expression and binds to multiple conserved noncoding sequences across the Ifng

Natsuki Fukuoka1, Misuzu Harada1, Ai Nishida1

  • 1Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|January 11, 2016
PubMed
Summary

Eomesodermin (Eomes) induces interferon-gamma (IFN-γ) production in cells lacking T-bet. Eomes binds the Ifng promoter and regulatory regions, influencing IFN-γ expression.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • T-box transcription factors T-bet and eomesodermin (Eomes) regulate interferon-gamma (IFN-γ) expression.
  • The specific role of Eomes in IFN-γ expression is not fully understood.

Purpose of the Study:

  • Investigate the Eomes-dependent regulation of IFN-γ expression.
  • Determine how Eomes interacts with the Ifng locus.

Main Methods:

  • Ectopic expression of Eomes in T-bet/Eomes-negative mouse cell lines (BW5147, EL4).
  • Luciferase reporter assays using the Ifng promoter.
  • Chromatin immunoprecipitation (ChIP) assays.
  • Analysis of histone modifications.

Main Results:

  • Ectopic Eomes expression induced IFN-γ production in response to PMA/IM stimulation.
  • Eomes bound to the Ifng promoter and conserved noncoding sequences (CNSs).
  • Eomes increased permissive histone modifications at the Ifng locus.
  • Stimulation enhanced Eomes binding to specific CNSs.

Conclusions:

  • Eomes directly regulates IFN-γ expression by binding to the Ifng promoter and CNSs.
  • Eomes binding is both constitutive and inducible, modulated by cellular stimulation.
  • Eomes plays a significant role in controlling IFN-γ production.