IDENTIFICATION OF A GLUCOCORTICOID RESPONSE ELEMENT IN THE HUMAN GAMMA-CHAIN FIBRINOGEN PROMOTER

The effect of the synthetic glucocorticoid hormone dexamethasone on hu man gamma chain fibrinogen gene expression was examined. The whole pro moter region of 3.8 kb of this gene and progressive 5'-deletions were inserted into a promoterless expression vector, upstream of the lucife rase gene and transiently transfected into the human hepatoma HepG2 ce lls, in the presence or in the absence of dexamethasone stimulation. D eletion analysis allowed to identify a region located between -1359 an d -954 bp upstream from the transcription start site, involved in horm one inducibility. On the basis of a computer-assisted analysis, a puta tive GRE was found in this region at bases -1116 to -1102. Specific po int mutations eliminating this putative GRE led to complete loss of gl ucocorticoid inducibility, thus indicating its functional role. Bindin g of the rat glucocorticoid receptor to this site was demonstrated by mobility-shift assays.