Presence of functional cyclic AMP responsive element in the 3'-untranslated region of the human thrombomodulin gene.

We characterized the transcriptional regulatory function of the 3'-untranslated region of the thrombomodulin gene by transient transfection assays in human umbilical endothelial cells. Deletion analyses of the 3'-untranslated region indicated that the region containing the consensus sequence of the cyclic AMP (cAMP) responsive element (position 2092) showed an increased transcriptional activity in response to cAMP. Gel-shift analysis showed that a band representing the fragment containing position 2092 was retarded when incubated with nuclear extracts from the cells treated with cAMP. In addition, the region downstream of the cAMP responsive element was found to function negatively in the gene expression. These results indicate that the 3'-untranslated region has a functional cAMP responsive element and plays an important role in the regulation of the thrombomodulin gene expression.