Induction of interferon-beta gene expression by dexamethasone in murine L929 cells.
Glucocorticoids bind to their receptors and trigger the transcriptional activation or repression of target genes by binding to DNA sequences, the glucocorticoid responsive element (GRE). The murine interferon-beta (Mu-IFN beta) gene in L929 cells can be induced by dexamethasone to give both transcription and translation products specific to murine IFN beta. The 3'-noncoding region of the Mu-IFN beta gene was found to contain a GRE very similar to the consensus GRE sequence involved in glucocorticoid-regulated genes. Gel retardation assays showed that the oligonucleotide corresponding to that GRE competed with the MMTV GRE oligonucleotide for glucocorticoid receptor binding and was supershifted by human antiglucocorticoid receptor antibodies. Transiently transfected murine cells (L929) with the GRE-IFN beta 3' sequence inserted upstream of the thymidine kinase promoter and the chloramphenicol acetyl transferase gene treated with dexamethasone with or without the antiglucocorticoid RU486 and their chloramphenicol acetyl transferase activity assayed, show that this GRE is efficient. We conclude that the Mu-IFN beta gene in L929 murine cells can be induced by dexamethasone, and that the hormone effect may be mediated by the 3'-GRE sequence.
Soury
B
B
Unité Propre de Recherche 37 Centre National de la Recherche Scientifique, Université René Descartes Paris V, France.
Hentzen
D
D
Vignal
M
M
Christeff
N
N
Doly
J
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D016899:Interferon-beta; D003907:Dexamethasone