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1: Nat Immunol. 2001 Jan;2(1):51-7.Click here to read Links
Comment in:
Nat Immunol. 2001 Jan;2(1):9-10.

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

Weinmann AS, Mitchell DM, Sanjabi S, Bradley MN, Hoffmann A, Liou HC, Smale ST.

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.

PMID: 11135578 [PubMed - indexed for MEDLINE]