Role of the composite glucocorticoid response element in proliferin gene expression

A binding site for the glucocorticoid receptor in the serum-inducible proliferin gene promoter has been reported to function as a composite glucocorticoid response element when fused to a minimal promoter. We now show that this element can also act as a glucocorticoid-independent negative regulator of transcription, both as an isolated element fused to a minimal promoter and within the context of the proliferin gene promoter. Furthermore, this element is recognized by a factor in mouse fibroblast cell extracts that is distinct from the glucocorticoid receptor and from AP-1, both of which have previously been shown to be able to bind to this site. The ability of this element to repress serum-inducible proliferin promoter activity is dependent on the position of this element with respect to the adjacent serum response region, and on the activity of a positive regulatory element located further upstream in the proliferin promoter.