Human beta-fibrinogen gene expression. Upstream sequences involved in its tissue specific expression and its dexamethasone and interleukin 6 stimulation.
The synthesis of fibrinogen in the liver is drastically enhanced during the inflammatory process. Two factors are involved: glucocorticoids and the hepatocyte stimulating factor which is identical with interleukin 6 (Il6), also called interferon beta 2. The function of the 5'-flanking region of the human beta-fibrinogen (beta-Fg) gene has been studied by deletion analysis with the chloramphenicol acetyltransferase (CAT) gene as a transient expression vector. In this analysis, a fragment containing 150 base pairs (bp) upstream from the cap site is sufficient to drive expression of the CAT gene in the hepatoma cells HepG2, but not in HeLa cells. The beta-Fg gene is induced by dexamethasone and Il6 in HepG2. We identify a domain located between -2900 and -1500 bp upstream from the transcription start point involved in dexamethasone sensibility. This distal regulatory region can confer hormone inductibility to a heterologous promoter and exert its effect in either orientation. The sequence located between -150 and -82 bp upstream from the transcription start point is responsive for the Il6-stimulated expression. This 68-bp sequence contains probably all the cis-acting Il6-responsive element of the human beta-Fg gene.
Huber
P
P
Département de Recherche, Fondamentale, Centre d'Etudes Nucléaires 85X, Grenoble, France.
Laurent
M
M
Dalmon
J
J
D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D003907:Dexamethasone / Q000494:pharmacology; D005340:Fibrinogen / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins; D015183:Restriction Mapping; D014162:Transfection
D015850:Interleukin-6; D011994:Recombinant Proteins; D003907:Dexamethasone; D005340:Fibrinogen; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase