Dexamethasone stimulates human A(1) adenosine receptor (A(1)AR) gene expression through multiple regulatory sites in promoter B

The expression of the human A(1) adenosine receptor gene is controlled by t wo promoters, promoters A and B, and they are located 600 base pairs apart. The characteristics of the two promoters differ by the activity of express ion, tissue specificity, and the potential regulatory elements around them, Promoter A is more active but its expression is observed only in selected tissues, whereas promoter B is constitutively expressed but at much reduced levels. In Chinese hamster ovary (CHO) cells transiently transfected with plasmids containing either promoter linked to a reporter gene, dexamethason e (dex) can stimulate (or enhance) the expression of promoter B much more e ffectively than that of promoter A. Mutation and deletion studies on plasmi ds containing promoter B have shown that the stimulation is mediated throug h multiple regulatory sites, including a serum response element, AP1, and T ATA box. However, a single-glucocorticoid response element monomer-binding site between promoters A and B does not have significant contribution to de x-regulated expression. The interactions between glucocorticoid receptor (G R) and some regulatory sites are probably occurring via this protein (GR) i nteracting with other DNA-binding proteins because there is no GR DNA-bindi ng sequence in the sites studied. The stimulation can be eliminated by mife pristone, an antagonist of GR, indicating the involvement of GR in gene reg ulation. In addition, dex treatment also stimulated the expression of A(1) adenosine receptors in CHO cells transfected with the plasmids containing c ontiguous genomic sequences of promoter B or promoters A and B linked to th e receptor-coding sequence. When promoter A is active and both promoter A a nd B are present in a construct, dex treatment induced a much smaller perce ntage of stimulation.