CHARACTERIZATION OF SOMATOSTATIN TRANSACTIVATING FACTOR-I, A NOVEL HOMEOBOX FACTOR THAT STIMULATES SOMATOSTATIN EXPRESSION IN PANCREATIC-ISLET CELLS

The endocrine pancreas consists of several differentiated cell types t hat are distinguished by their selective expression of peptide hormone s such as insulin, glucagon, and somatostatin. Although a number of ho meobox-type factors have been proposed as key regulators of individual peptide genes in the pancreas, their cellular distribution and relati ve abundance remain uncharacterized. Also, their overlapping DNA bindi ng specificities have further obscured the regulatory functions these factors perform during development. In this report we characterize a n ovel homeobox-type somatostatin transactivating factor termed STF-1, w hich is uniformly expressed in cells of the endocrine pancreas and sma ll intestine. The 283-amino acid STF-1 protein binds to tissue-specifi c elements within the somatostatin promoter and stimulates somatostati n gene expression both in vivo and in vitro. Remarkably, STF-1 compris es the predominant tissue-specific element-binding activity in nuclear extracts from somatostatin-producing pancreatic islet cells, suggesti ng that this protein may have a primary role in regulating peptide hor mone expression and specifying endocrine cell lineage in the developin g gut.