Identification of a Glucocorticoid Response Element in the Human γ Chain Fibrinogen Promoter

Rosanna Asselta; Stefano Duga; Michele Modugno; Massimo Malcovati; Maria Luisa Tenchini

doi:10.1055/s-0037-1615031

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(06): 1144-1150
DOI: 10.1055/s-0037-1615031

Rapid Communication

Schattauer GmbH

Identification of a Glucocorticoid Response Element in the Human γ Chain Fibrinogen Promoter

Rosanna Asselta

From the Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy

,

Stefano Duga

From the Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy

,

Michele Modugno

From the Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy

,

Massimo Malcovati

From the Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy

,

Maria Luisa Tenchini

From the Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy

› Author Affiliations

Abstract

Summary

The effect of the synthetic glucocorticoid hormone dexamethasone on human γ chain fibrinogen gene expression was examined. The whole promoter region of 3.8 kb of this gene and progressive 5’-deletions were inserted into a promoterless expression vector, upstream of the luciferase gene and transiently transfected into the human hepatoma HepG2 cells, in the presence or in the absence of dexamethasone stimulation. Deletion analysis allowed to identify a region located between –1359 and –954 bp upstream from the transcription start site, involved in hormone inducibility. On the basis of a computer-assisted analysis, a putative GRE was found in this region at bases –1116 to –1102. Specific point mutations eliminating this putative GRE led to complete loss of glucocorticoid inducibility, thus indicating its functional role. Binding of the rat glucocorticoid receptor to this site was demonstrated by mobility-shift assays.

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References

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