Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event

Academic Article

Abstract

  • Lipopolysaccharide (LPS) induction of the gene encoding interleukin 12 p40 requires remodeling of a promoter-encompassing nucleosome and the Toll-like receptor (TLR)-mediated activation of a c-Rel-containing complex. Analysis of TLR4-mutant mice revealed that remodeling requires TLR signaling. However, Rel proteins and other proteins required for transcription of an integrated p40 promoter were insufficient for remodeling. c-Rel was also unnecessary for remodeling, as remodeling was observed in c-Rel-/- macrophages, which lack p40 transcripts. These results suggest that remodeling requires TLR signaling pathways that diverge from the c-Rel activation pathways. The factors that stimulate remodeling may represent, therefore, newly identified targets of TLR signaling and of agents that regulate inflammatory responses and TH1 development.
  • Published In

  • Nature Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Weinmann AS; Mitchell DM; Sanjabi S; Bradley MN; Hoffmann A; Liou HC; Smale ST
  • Start Page

  • 51
  • End Page

  • 57
  • Volume

  • 2
  • Issue

  • 1