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Cooperative NCoR/SMRT interactions establish a corepressor-based strategy for integration of inflammatory and

Serena Ghisletti1, Wendy Huang, Kristen Jepsen

  • 1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA.

Genes & Development
|March 21, 2009
PubMed

Insights

Nuclear receptor corepressors (NCoR) and SMRT establish gene repression checkpoints. Their selective recruitment and mutual dependence control inflammatory gene activation, crucial for immunity and homeostasis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • Innate immune responses require rapid gene activation during infection.
  • Mechanisms of inflammatory gene repression and derepression are not fully understood.
  • Nuclear receptor corepressors (NCoR) and SMRT are key regulators of gene expression.

Purpose of the Study:

  • To investigate the roles of NCoR and SMRT in regulating inflammatory genes.
  • To elucidate the mechanisms of corepressor recruitment and function in macrophages.
  • To understand how inflammatory and anti-inflammatory signals are integrated.

Main Methods:

  • Analysis of gene expression in macrophages.
  • Investigating the recruitment of NCoR and SMRT to specific gene promoters.
  • Studying the functional interactions between corepressors and transcription factors like c-Jun and Tel.

Main Results:

  • NCoR and SMRT establish repression checkpoints on inflammatory genes.
  • Selective recruitment of NCoR and SMRT via c-Jun or Tel creates distinct regulatory networks.
  • Mutual dependence of NCoR and SMRT binding is required for LXR transrepression.
  • Inflammatory pathways targeting NCoR or SMRT can derepress NCoR/SMRT-dependent genes.

Conclusions:

  • NCoR and SMRT play critical, coordinated roles in controlling inflammatory gene expression.
  • A combinatorial corepressor strategy integrates immune and homeostatic signals.
  • These findings provide insights into the regulation of immunity and inflammation.

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