Cooperative NCoR/SMRT interactions establish a eorepressor-based strategy for integration of inflammatory ana anti-inflammatory signaling pathways

Serena Ghisletti, Wendy Huang, Kristen Jepsen, Chris Benner, Gary Hardiman, Michael G. Rosenfeld, Christopher K. Glass

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Innate immune responses to bacterial or viral infection require rapid transition of large cohorts of inflammatory response genes from poised/repressed to actively transcribed states, but the underlying repression/derepression mechanisms remain poorly understood. Here, we report that, while the nuclear receptor corepressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) corepressors establish repression checkpoints on broad sets of inflammatory response genes in macrophages and are required for nearly all of the transrepression activities of liver X receptors (LXRs), they can be selectively recruited via e-Jun or the Ets repressor Tel, respectively, establishing NCoR-specific, SMRT-specific, and NCoR/SMRT-dependent promoters. Unexpectedly, the binding of NCoR and SMRT to NCoR/SMRT-dependent promoters is frequently mutually dependent, establishing a requirement for both proteins for LXR transrepression and enabling inflammatory signaling pathways that selectively target NCoR or SMRT to also derepress/activate NCoR/SMRT-dependent genes. These findings reveal a combinatorial, corepressor-based strategy for integration of inflammatory and anti-inflammatory signals that play essential roles in immunity and homeostasis.

Original languageEnglish
Pages (from-to)681-693
Number of pages13
JournalGenes and Development
Volume23
Issue number6
DOIs
Publication statusPublished - 15 Mar 2009
Externally publishedYes

Keywords

  • Cjun
  • Inflammatory genes
  • NCoR
  • P50
  • SMRT
  • TEL

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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