Egr-1 and Sp1 interact functionally with the 5-lipoxygenase promoter and its naturally occurring mutants

Am J Respir Cell Mol Biol. 1998 Aug;19(2):316-23. doi: 10.1165/ajrcmb.19.2.3154.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / genetics*
  • Binding Sites
  • Cell Line
  • DNA Footprinting
  • DNA-Binding Proteins / metabolism*
  • Drosophila
  • Mutation*
  • Promoter Regions, Genetic*
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Sp1 Transcription Factor / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Zinc Fingers


  • DNA-Binding Proteins
  • Recombinant Proteins
  • Sp1 Transcription Factor
  • Transcription Factors
  • Arachidonate 5-Lipoxygenase