Functional characterization of a novel promoter element required for an innate immune response in Drosophila.
Innate immune reactions are crucial processes of metazoans to protect the organism against overgrowth of faster replicating microorganisms. Drosophila melanogaster is a precious model for genetic and molecular studies of the innate immune system. In response to infection, the concerted action of a battery of antimicrobial peptides ensures efficient killing of the microbes. The induced gene expression relies on translocation of the Drosophila Rel transcription factors Relish, Dif, and Dorsal to the nucleus where they bind to kappaB-like motifs in the promoters of the inducible genes. We have identified another putative promoter element, called region 1 (R1), in a number of antimicrobial peptide genes. Site-directed mutagenesis of the R1 site diminished Cecropin A1 (CecA1) expression in transgenic Drosophila larvae and flies. Infection of flies induced a nuclear R1-binding activity that was unrelated to the kappaB-binding activity in the same extracts. Although the R1 motif was required for Rel protein-mediated CecA1 expression in cotransfection experiments, our data argue against it being a direct target for the Drosophila Rel proteins. We propose that the R1 and kappaB motifs are targets for distinct regulatory complexes that act in concert to promote high levels of antimicrobial peptide gene expression in response to infection.
Department of Molecular Biology and Functional Genomics, Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
Hanna
H
Uvell
Ylva
Y
Engström
D000818:Animals; D030801:Animals, Genetically Modified; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000276:immunology*; D015870:Gene Expression; D017344:Genes, Insect; D007113:Immunity, Innate / Q000235:genetics*; D007239:Infections / Q000235:genetics / Q000276:immunology; D007763:Lac Operon; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic
D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; C031161:cecropin A; D004247:DNA