Egr-1 and Sp1 Interact Functionally with the 5-Lipoxygenase Promoter and Its Naturally Occurring Mutants

摘要: 5-Lipoxygenase (5-LO), an enzyme essential for the formation of leukotrienes, is functionally modulated by a number mechanisms, including transcriptional controls. The 5-LO promoter has unique G+C-rich sequence, located between 176 and 147 base pairs upstream ATG translation start site, which contains five tandem Sp1 (a zinc-finger transcription factor) consensus binding sites overlapping early growth response protein 1 (Egr-1), factor, sites. A family naturally occurring mutations been identified that consists additions or deletions these role Sp1/Egr-1 in regulation effects on regulatory mechanisms are unknown. We now show Egr-1 bind specifically to sequence using vitro deoxyribonuclease I footprinting. Both activate promoter-reporter constructs minimally active drosophila SL2 cotransfection system, involved this process. Moreover, studies comparing mutant function indicate both trans-activation proportional within sequence. It possible basal inducible gene transcriptions mediated interplay Sp1, Egr-1, other factors region, alter modifying their potential.