Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells.
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.
Leonard
J
J
Clayton Foundation Laboratories for Peptide Biology, La Jolla, California 92037.
Peers
B
B
Johnson
T
T
Ferreri
K
K
Lee
S
S
Montminy
M R
MR
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005801:Genes, Homeobox; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics*; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D013004:Somatostatin; D012313:RNA; D004247:DNA