INTERACTION OF THE TRANSCRIPTION FACTOR CREB WITH PANCREATIC-ISLET CELL-SPECIFIC ENHANCER ELEMENTS

The cAMP-responsive element (CRE)-binding transcription factor CREB co nfers basal as well as cAMP- and calcium-induced transcription. Activa tion of CREB occurs by phosphorylation on serine-119 stimulating its t ransactivating potency. However, the regulation of CREB-DNA binding by posttranslational modification is not established, In this study, usi ng binding and functional assays, the interaction of CREB with pancrea tic islet cell-specific enhancer elements of the rat somatostatin (SMS -UE), glucagon (Glu-G3) and insulin I genes (Ins-E1) was investigated, which share a functional regulatory sequence, PISCES, with islet-spec ific activity. CREB bound to the SMS-UE, Bacterially expressed recombi nant CREB bound equally well to the SMS-LIE and to the somatostatin CR E, However, cellular CRE-binding proteins with CREB-like immunoreactiv ity recognized the SMS-UE markedly less well than the somatostatin CRE suggesting the existence of a posttranslational modification of CREB that alters its binding specificity.