Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells.

TLDR

The endocrine pancreas contains distinct hormone‑producing cells, yet the distribution, abundance, and overlapping DNA‑binding specificities of homeobox regulators that control peptide gene expression remain poorly defined. This study aims to characterize a novel homeobox transcription factor, STF‑1, that transactivates somatostatin expression in pancreatic islet and intestinal cells. STF‑1, a 283‑amino‑acid homeobox protein expressed throughout the endocrine pancreas and small intestine, binds somatostatin promoter elements to activate transcription in vivo and in vitro. STF‑1 constitutes the dominant tissue‑specific DNA‑binding activity in nuclear extracts from somatostatin‑producing islet cells, indicating a primary role in regulating peptide hormone expression and endocrine lineage specification during gut development.

Abstract

The endocrine pancreas consists of several differentiated cell types that are distinguished by their selective expression of peptide hormones such as insulin, glucagon, and somatostatin. Although a number of homeobox-type factors have been proposed as key regulators of individual peptide genes in the pancreas, their cellular distribution and relative abundance remain uncharacterized. Also, their overlapping DNA binding specificities have further obscured the regulatory functions these factors perform during development. In this report we characterize a novel homeobox-type somatostatin transactivating factor termed STF-1, which is uniformly expressed in cells of the endocrine pancreas and small intestine. The 283-amino acid STF-1 protein binds to tissue-specific elements within the somatostatin promoter and stimulates somatostatin gene expression both in vivo and in vitro. Remarkably, STF-1 comprises the predominant tissue-specific element-binding activity in nuclear extracts from somatostatin-producing pancreatic islet cells, suggesting that this protein may have a primary role in regulating peptide hormone expression and specifying endocrine cell lineage in the developing gut.