A CLASSICAL ENHANCER ELEMENT RESPONSIVE TO BOTH LIPOPOLYSACCHARIDE AND INTERFERON-GAMMA AUGMENTS INDUCTION OF THE INOS GENE IN MOUSE MACROPHAGES

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.