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Chromatin Immunoprecipitation (ChIP) to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells
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ERK1 and ERK2 activate CCAAAT/enhancer-binding protein-beta-dependent gene transcription in response to

J Hu1, S K Roy, P S Shapiro

  • 1Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

The Journal of Biological Chemistry
|September 21, 2000
PubMed

Insights

Interferon-gamma (IFN-gamma) activates a novel pathway involving extracellular signal-regulated kinases (ERKs) to regulate gene expression via C/EBP-beta. This pathway is independent of JAK1, highlighting a new mechanism in IFN signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Interferons (IFNs) modulate cellular gene expression primarily through the JAK-STAT pathway.
  • CCAAAT/enhancer-binding protein-beta (C/EBP-beta) interacts with a novel IFN-gamma-activated transcriptional element (GATE) to induce gene transcription.

Purpose of the Study:

  • To elucidate a new IFN-gamma-stimulated signaling pathway regulating C/EBP-beta-dependent gene expression.
  • To investigate the role of extracellular signal-regulated kinases (ERKs) in IFN-gamma signaling.

Main Methods:

  • Utilized mutant MKK1, inhibitors, and mutant ERK to assess pathway involvement.
  • Examined the correlation between ERK activation and C/EBP-beta-dependent gene expression.
  • Investigated the requirement for STAT1 and JAK1 in C/EBP-beta-induced gene expression.

Main Results:

  • IFN-gamma activates ERKs, which stimulate C/EBP-beta-dependent gene expression via the GATE element.
  • Sustained ERK activation correlated directly with C/EBP-beta-mediated gene induction.
  • C/EBP-beta-induced gene expression required STAT1 but not JAK1.
  • A C/EBP-beta mutant lacking an ERK phosphorylation site failed to induce IFN-stimulated gene expression.

Conclusions:

  • Identified a novel IFN-gamma signaling pathway linking C/EBP-beta to gene expression through ERK activation, independent of JAK1.
  • This pathway emphasizes the crucial role of ERKs in mediating IFN-gamma responses.
  • The findings reveal a new layer of complexity in interferon-mediated gene regulation.

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