A novel lipopolysaccharide-response element contributes to induction of nitric oxide synthase.
The gene encoding the high output isoform of nitric oxide synthase represents a large class of alarm and defense genes transcriptionally induced in response to bacterial lipopolysaccharide (LPS). The promoters of most of these genes contain at least two LPS-response elements, one of which commonly binds transcription factors of the NF-kappaB/Rel family. Here a novel LPS-response element is identified in the inducible nitric oxide synthase promoter, termed LREAA, which contains critical adenosine residues lying 19-20 base pairs downstream of the proximal NF-kappaB binding element (NFkappaBd). Both NFkappaBd and LREAA are required for LPS-induced promoter activity. A protein partially recognized by antibody against transcription factor Oct-1 binds to the LREAA element constitutively in untreated macrophages while contributing to a DNA-protein complex that includes NF-kappaB p50 in macrophages treated with LPS. NF-kappaB p50 and the LREAA-binding proteins may together recruit an LPS-triggered transactivator of transcription.
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Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021, USA. qwxie@med.cornell.edu
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002374:Catalase / Q000096:biosynthesis; D002460:Cell Line; D004790:Enzyme Induction; D017930:Genes, Reporter; D007527:Isoenzymes / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D007527:Isoenzymes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D002374:Catalase; D019001:Nitric Oxide Synthase