Egr-1 and Sp1 interact functionally with the 5-lipoxygenase promoter and its naturally occurring mutants.
Publication/Presentation Date
8-1-1998
Abstract
5-Lipoxygenase (5-LO), an enzyme essential for the formation of leukotrienes, is functionally modulated by a number of mechanisms, including transcriptional controls. The 5-LO promoter has a unique G+C-rich sequence, located between 176 and 147 base pairs upstream of the ATG translation start site, which contains five tandem Sp1 (a zinc-finger transcription factor) consensus binding sites overlapping five tandem early growth response protein 1 (Egr-1), a zinc-finger transcription factor, consensus binding sites. A family of naturally occurring mutations has been identified that consists of additions or deletions of these binding sites. The role of these overlapping Sp1/Egr-1 sites in the regulation of 5-LO transcription and the effects of these mutations on transcriptional regulatory mechanisms are unknown. We now show that Sp1 and Egr-1 bind specifically to the G+C-rich promoter sequence using in vitro deoxyribonuclease I footprinting. Both Sp1 and Egr-1 activate 5-LO promoter-reporter constructs in a minimally active drosophila SL2 cotransfection system, and the G+C-rich sequence is involved in this process. Moreover, studies comparing mutant promoter function indicate that both Sp1 and Egr-1 trans-activation are proportional to the number of Sp1/Egr-1 consensus binding sites within the G+C-rich sequence. It is possible that basal and inducible 5-LO gene transcriptions are mediated by an interplay of Sp1, Egr-1, and other transcription factors within the G+C-rich promoter region, and the naturally occurring mutations alter transcription by modifying their trans-activation potential.
Volume
19
Issue
2
First Page
316
Last Page
323
ISSN
1044-1549
Published In/Presented At
Silverman, E. S., Du, J., De Sanctis, G. T., Rådmark, O., Samuelsson, B., Drazen, J. M., & Collins, T. (1998). Egr-1 and Sp1 interact functionally with the 5-lipoxygenase promoter and its naturally occurring mutants. American journal of respiratory cell and molecular biology, 19(2), 316–323. https://doi.org/10.1165/ajrcmb.19.2.3154
Disciplines
Medicine and Health Sciences
PubMedID
9698605
Department(s)
Department of Medicine
Document Type
Article