Inducibility of E4BP4 suggests a novel mechanism of negative gene regulation by glucocorticoids.

The major biological effects of glucocorticoids are thought to be initiated through changes in the expression of cellular genes. However, the mechanisms involved in the suppression of some gene products by glucocorticoids are not well defined. ID13 mouse fibroblast cells were treated with the synthetic glucocorticoid dexamethasone (Dex) or with vehicle. Plus/ minus (+Dex/-Dex) cDNAs were used to screen an ID13 cDNA library. Using this method, we found that the recently identified human protein adenovirus E4 promoter binding protein (E4BP4) mRNA was induced by Dex in the ID13 cell line. E4BP4 is a transcriptional repressor and binds to a specific DNA element. Further investigation indentified E4BP4-like DNA elements located in the promoters of glucocorticoid repressed genes Cox-2, iNOS, and cPLA2. These findings suggest that E4BP4 may play a role in the glucocorticoid repression of these and other genes.