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

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-Re1-containing complex. Analysis of TLR4-mutant mice revealed that remodeling requires TLR signaling. Howev er, Re1 proteins and other proteins required for transcription of an integr ated p40 promoter were insufficient for remodeling. c-Re1 was also unnecess ary for remodeling, as remodeling was observed in c-Re1(-/-) macrophages, w hich lack p40 transcripts. These results suggest that remodeling requires T LR signaling pathways that diverge from the c-Re1 activation pathways. The factors that stimulate remodeling may represent, therefore, newly identifie d targets of TLR signaling and of agents that regulate inflammatory respons es and T(H)1 development.