title: A classical enhancer element responsive to both lipopolysaccharide and interferon-gamma augments induction of the iNOS gene in mouse macrophages.
abstract: The ability of macrophages to kill some kinds of tumor cells is dependent upon the production of the free radical nitric oxide (NO) by the inducible enzyme NO synthase (iNOS; EC 1.14.13.39). Expression of the iNOS gene is induced by lipopolysaccharide (LPS) and augmented by interferon-gamma (IFN-gamma). Two regions of the iNOS promoter are known to regulate induction, a promoter proximal region I (RI) and a more distal region II (RII). Reconfiguration of RI within the iNOS regulatory region revealed its dependence upon native position and orientation for maximal activity, suggesting that it is a core promoter module, and further implicated the putative octamer element as a contributor to promoter activity. RII, however, functioned in a relatively orientation- and position-independent manner. Therefore, it had the characteristics of a classical enhancer element.
authors.affiliation: Wilkinson Laboratory for Cancer Research, University of Kansas Cancer Center, Kansas City 66160-7184, USA.
authors.forename: E W
authors.initials: EW
authors.lastname: Alley
authors.forename: W J
authors.initials: WJ
authors.lastname: Murphy
authors.forename: S W
authors.initials: SW
authors.lastname: Russell
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D000818:Animals; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D004790:Enzyme Induction; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D008070:Lipopolysaccharides; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases