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-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.
Weinmann
A S
AS
Howard Hughes Medical Institute and Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, CA 90095-1662, USA.
Mitchell
D M
DM
Sanjabi
S
S
Bradley
M N
MN
Hoffmann
A
A
Liou
H C
HC
Smale
S T
ST
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D004262:DNA Restriction Enzymes / Q000378:metabolism; D029721:Drosophila Proteins; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D022762:CCAAT-Enhancer-Binding Proteins; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D009707:Nucleosomes; D020569:Proto-Oncogene Proteins c-rel; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018664:Interleukin-12; D004262:DNA Restriction Enzymes