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A classical enhancer element responsive to both lipopolysaccharide and interferon-gamma augments induction of the
E W Alley1, W J Murphy, S W Russell
1Wilkinson Laboratory for Cancer Research, University of Kansas Cancer Center, Kansas City 66160-7184, USA.
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.