Hepatocyte-stimulating factor, beta 2 interferon, and interleukin-1 enhance expression of the rat alpha 1-acid glycoprotein gene via a distal upstream regulatory region.
The rat alpha 1-acid glycoprotein (AGP) gene is transcriptionally regulated by dexamethasone, interleukin 1 (IL-1), hepatocyte-stimulating factor, and beta 2 interferon. The steroid and peptide hormones stimulate expression of the AGP gene synergistically as well as independently. The regulatory sequence responsible for dexamethasone-stimulated expression has been localized previously to a region that is 120 to 64 base pairs (bp) upstream of the transcription start site (H. Baumann and L. E. Maquat, Mol. Cell. Biol. 6:2551-2561, 1986). To identify the regulatory sequence that is responsive to the peptide hormones, different lengths of the AGP gene 5'-flanking DNA were linked to the chloramphenicol acetyltransferase gene and then assayed for hormone-inducible chloramphenicol acetyltransferase gene expression in transiently transfected HepG2 cells. We demonstrate that an enhancer region that is responsive to IL-1, hepatocyte-stimulating factor, and beta 2 interferon lies within a 142-bp sequence located 5,300 to 5,150 bp upstream of the transcription start site. This distal regulatory region can confer hormone inducibility to a heterologous promoter; exert its affect in either orientation; and function, to a lesser degree, in nonhepatic but IL-1-responsive cells.
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6; D008969:Molecular Sequence Data; D009961:Orosomucoid / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000502:physiology*; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid
D000209:Acute-Phase Proteins; D007370:Interferon Type I; D007375:Interleukin-1; D015850:Interleukin-6; D009961:Orosomucoid; D011506:Proteins; D003907:Dexamethasone