Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event
Abstract
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 T_H1 development.
Additional Information
© 2001 Nature Publishing Group. Received 11 September 2000; accepted 27 October 2000. We thank S. Plevy for providing the RAW264.7 cell lines containing the stably integrated p40 promoter-CAT reporter plasmids,V. Schuman, S. Sea and J. Park for maintaining mouse colonies and D. Baltimore, D.Thanos and R. Modlin for helpful discussions and critical reading of the manuscript. Supported by US Public Health Service grants GM07185 (to A. S.W. and M. N. B.) and AI07323 (to S. S.) and a University of California Dissertation-Year Fellowship (to A. S.W.). S.T. S. is an Investigator with the Howard Hughes Medical Institute.Additional details
- Eprint ID
- 56482
- Resolver ID
- CaltechAUTHORS:20150408-110349968
- GM07185
- U.S. Public Health Service
- AI07323
- U.S. Public Health Service
- University of California Dissertation-Year Fellowship
- Howard Hughes Medical Institute (HHMI)
- Created
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2015-04-08Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field