Nature Immunology
2, 51 - 57 (2001)
doi:10.1038/83168
Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent
eventAmy S. Weinmann1, Deborah M. Mitchell1, Shomyseh Sanjabi1, Michelle N. Bradley1, Alexander Hoffmann2, Hsiou-Chi Liou3
& Stephen T. Smale11
Howard Hughes Medical Institute and Department of Microbiology,
Immunology and Molecular Genetics, UCLA, Los Angeles,
CA 90095-1662, USA. 2
Department of Biology, California Institute of Technology
, Pasadena, CA 91125, USA.
3
Division of Immunology, Department of Medicine, Cornell
University Medical College, New York, NY 10021
, USA.
Correspondence should be addressed to Stephen T. Smale steves@hhmi.ucla.eduLipopolysaccharide (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.
|
