Genetic determinants of 5-lipoxygenase transcription

Background: 5 Lipoxygenase (5-LO) is a critical enzyme in the production of the leukotrienes, We have identified a series of mutations in the 5-LO gene that modify gene transcription. These mutations consist of addition of an Sp-l binding motif (-GGGCGG-) or deletion of one or two Sp-l binding motifs in the 5-LO core promoter. Methods: Mutant forms of the 5-LO core promoter were placed in a chloramphenicol acetyl transferase (CAT) reporter construct using either HeLa or SL-2 cells. Results: In HeLa cells all of the mutant forms are less effective in driving CAT reporter activity than the wild-type promoter. In SL-2 cells the construct containing the addition mutation was more effective in driving CAT reporter activity, while the constructs containing the deletion mutations were less effective. Conclusions: These data indicate that naturally occurring mutations in the 5-LO core promoter modify gene transcription in vitro.