[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Peers, Bernard ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Johnson, T.
Ferreri, K.
Lee, S.
Montminy, M. R.
Leonard, Jim
Language :
English
Title :
Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells.
Publication date :
1993
Journal title :
Molecular Endocrinology
ISSN :
0888-8809
eISSN :
1944-9917
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Wessells, N., Evans, J., Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas (1968) Dev Biol, 17, pp. 413-446
Alpert, S., Hanahan, D., Teitelman, G., Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply and relationship with neurons (1988) Cell, 53, pp. 295-308
Leonard, J., Serup, P., Gonzalez, G., Edlund, T., Montminy, M., The LIM family transcription factor lsl-1 requires cAMP response element binding protein to promote somatostatin expression in pancreatic islet cells (1992) Proc Natl Acad Sci USA, 89, pp. 6247-6251
Vallejo, M., Miller, C., Habener, J.F., Somatostatin gene transcription regulated by a bipartite pancreatic islet D-cell-specific enhancer coupled synergistically to a cAMP response element (1992) J Biol Chem, 267, pp. 12868-12875
Ohlssuri, H., Thor, S., Edlund, T., Novel insulin promoter-and enhancer-binding proteins that discriminate between pancreatic α and β-cells (1991) Mol Endocrinol, 5, pp. 897-903
Scott, M., Tamkun, J.W., Hartzell, G.W., The structure of the homeodomain (1989) Biochim Biophys Acta, 989, pp. 25-48
Gehring, W., The homcobox in perspective (1992) Trends Biochem Sei, 17, pp. 277-280
Wedeen, C.J., Kostriken, R.G., Matsumura, I., Weisblat, D.A., Evidtsnut
fut a new family of evoutiunarily conserved homeobox genes (1990) Nucleic Acids Res, 18, p. 1908
Wright, C., Schnegelsberg, P., Derobertis, E.M., XIHbox 8: A novel Xenopus horneo protein restricted to a narrow band of endoderm (1988) Development, 104, pp. 787-794
Lee, S., Imaki, T., Vale, W., Rivier, C.R., Effect of prenatal exposure to ethanol on the activity of hypothalamic-pituitary-adrenal axis of the offspring: Impartance of the time nf exposure to ethnol and possible modulating mechanisms (1990) Mol Cell Neurosci, 1, pp. 168-177
Yamamoto, K.K., Gonzalez, G.A., Menzel, P., Rivier, J., Mont-Miny, M.R., Characterization of a bipartite activator domain in transcription factor CREB (1990) Cell, 60, pp. 611-617
Gonzalez, G.A., Menzel, P., Leonard, J., Fischer, W.H., Mont-Miny, M.R., Characterization of motifs which are critical for activity of the cyclic AMP-responsive transcription factor CREB (1991) Mol Cell Biol, 11, pp. 1306-1312