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Nat Immunol. 2001 Jan;2(1):51-7.

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

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Howard Hughes Medical Institute and Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA 90095-1662, USA.


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.

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