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Functional characterization of the transactivation properties of the PDX-1 homeodomain protein.
Peshavaria M
,
Henderson E
,
Sharma A
,
Wright CV
,
Stein R
.
???displayArticle.abstract??? Pancreas formation is prevented in mice carrying a null mutation in the PDX-1 homeoprotein, demonstrating a key role for this factor in development. PDX-1 can also bind to and activate transcription from cis-acting regulatory sequences in the insulin and somatostatin genes, which are expressed in pancreatic islet beta and delta cells, respectively. In this study, we compared the functional properties of PDX-1 with those of the closely related Xenopus homeoprotein XIHbox8. Analysis of chimeras between PDX-1, XIHbox8, and the DNA-binding domain of the Saccharomyces cerevisiae transcription factor GAL4 revealed that their transactivation domain was contained within the N-terminal region (amino acids 1 to 79). Detailed mutagenesis of this region indicated that transactivation is mediated by three highly conserved sequences, spanning amino acids 13 to 22 (subdomain A), 32 to 38 (subdomain B), and 60 to 73 (subdomain C). These sequences were also required by PDX-1 to synergistically activate insulin enhancer-mediated transcription with another key insulin gene activator, the E2A-encoded basic helix-loop-helix E2-5 and E47 proteins. These results indicated that N-terminal sequences conserved between the mammalian PDX-1 and Xenopus XIHbox8 proteins are important in transcriptional activation. Stable expression of the PDX-1 deltaABC mutant in the insulin- and PDX-1-expressing betaTC3 cell line resulted in a threefold reduction in the rate of endogenous insulin gene transcription. Strikingly, the level of the endogenous PDX-1 protein was reduced to very low levels in these cells. These results suggest that PDX-1 is not absolutely essential for insulin gene expression in betaTC3 cells. We discuss the possible significance of these findings for insulin gene transcription in islet beta cells.
Ahlgren,
The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice.
1996, Pubmed
Ahlgren,
The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice.
1996,
Pubmed
Alpert,
Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons.
1988,
Pubmed
Andersson,
Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.
1989,
Pubmed
Aronheim,
Distribution and characterization of helix-loop-helix enhancer-binding proteins from pancreatic beta cells and lymphocytes.
1991,
Pubmed
Aronheim,
The E2A gene product contains two separable and functionally distinct transcription activation domains.
1993,
Pubmed
Bretherton-Watt,
Insulin upstream factor 1 and a novel ubiquitous factor bind to the human islet amyloid polypeptide/amylin gene promoter.
1996,
Pubmed
Chan,
The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein.
1994,
Pubmed
Cordle,
Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins.
1991,
Pubmed
Crowe,
Mutagenesis of the rat insulin II 5'-flanking region defines sequences important for expression in HIT cells.
1989,
Pubmed
De Krijger,
The midgestational human fetal pancreas contains cells coexpressing islet hormones.
1992,
Pubmed
Eckner,
Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation.
1996,
Pubmed
Efrat,
Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene.
1988,
Pubmed
Gamer,
Autonomous endodermal determination in Xenopus: regulation of expression of the pancreatic gene XlHbox 8.
1995,
Pubmed
,
Xenbase
German,
Two related helix-loop-helix proteins participate in separate cell-specific complexes that bind the insulin enhancer.
1991,
Pubmed
German,
The insulin gene promoter. A simplified nomenclature.
1995,
Pubmed
German,
The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes.
1992,
Pubmed
Gittes,
Onset of cell-specific gene expression in the developing mouse pancreas.
1992,
Pubmed
Guz,
Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.
1995,
Pubmed
,
Xenbase
Henthorn,
Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif.
1990,
Pubmed
Henthorn,
Sequence of the cDNA encoding ITF-1, a positive-acting transcription factor.
1990,
Pubmed
Jonsson,
Insulin-promoter-factor 1 is required for pancreas development in mice.
1994,
Pubmed
Kamei,
A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors.
1996,
Pubmed
Karlsson,
A mutational analysis of the insulin gene transcription control region: expression in beta cells is dependent on two related sequences within the enhancer.
1987,
Pubmed
Lee,
Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein.
1995,
Pubmed
,
Xenbase
Leonard,
Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells.
1993,
Pubmed
Lillie,
Transcription activation by the adenovirus E1a protein.
1989,
Pubmed
Lukinius,
Ultrastructural studies of the ontogeny of fetal human and porcine endocrine pancreas, with special reference to colocalization of the four major islet hormones.
1992,
Pubmed
MacFarlane,
Glucose modulates the binding activity of the beta-cell transcription factor IUF1 in a phosphorylation-dependent manner.
1994,
Pubmed
Massari,
The AD1 transactivation domain of E2A contains a highly conserved helix which is required for its activity in both Saccharomyces cerevisiae and mammalian cells.
1996,
Pubmed
,
Xenbase
Melloul,
Glucose modulates the binding of an islet-specific factor to a conserved sequence within the rat I and the human insulin promoters.
1993,
Pubmed
Miller,
IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene.
1994,
Pubmed
,
Xenbase
Naya,
Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor.
1995,
Pubmed
Nordeen,
A rapid, sensitive, and inexpensive assay for chloramphenicol acetyltransferase.
1987,
Pubmed
Offield,
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.
1996,
Pubmed
,
Xenbase
Ohlsson,
IPF1, a homeodomain-containing transactivator of the insulin gene.
1993,
Pubmed
Olson,
Reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to a supraphysiologic glucose concentration is associated with loss of STF-1 transcription factor expression.
1995,
Pubmed
Peers,
Insulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1.
1994,
Pubmed
Peers,
The pancreatic islet factor STF-1 binds cooperatively with Pbx to a regulatory element in the somatostatin promoter: importance of the FPWMK motif and of the homeodomain.
1995,
Pubmed
Peshavaria,
XIHbox 8, an endoderm-specific Xenopus homeodomain protein, is closely related to a mammalian insulin gene transcription factor.
1994,
Pubmed
,
Xenbase
Petersen,
Transcriptional regulation of the human insulin gene is dependent on the homeodomain protein STF1/IPF1 acting through the CT boxes.
1994,
Pubmed
Peyton,
Two distinct class A helix-loop-helix transcription factors, E2A and BETA1, form separate DNA binding complexes on the insulin gene E box.
1994,
Pubmed
Pictet,
The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells.
1976,
Pubmed
Quong,
A new transcriptional-activation motif restricted to a class of helix-loop-helix proteins is functionally conserved in both yeast and mammalian cells.
1993,
Pubmed
Robinson,
Expression of the trans-active factors that stimulate insulin control element-mediated activity appear to precede insulin gene transcription.
1994,
Pubmed
Robinson,
Isolation and characterization of a novel transcription factor that binds to and activates insulin control element-mediated expression.
1994,
Pubmed
Saiki,
Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase.
1988,
Pubmed
Schreiber,
Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.
1989,
Pubmed
Serup,
The homeodomain protein IPF-1/STF-1 is expressed in a subset of islet cells and promotes rat insulin 1 gene expression dependent on an intact E1 helix-loop-helix factor binding site.
1995,
Pubmed
Serup,
Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1.
1996,
Pubmed
Sharma,
Glucose-induced transcription of the insulin gene is mediated by factors required for beta-cell-type-specific expression.
1994,
Pubmed
Shieh,
Cell-specific and ubiquitous factors are responsible for the enhancer activity of the rat insulin II gene.
1991,
Pubmed
Stein,
Analysis of E1A-mediated growth regulation functions: binding of the 300-kilodalton cellular product correlates with E1A enhancer repression function and DNA synthesis-inducing activity.
1990,
Pubmed
Steiner,
Structure and evolution of the insulin gene.
1985,
Pubmed
Sun,
An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers.
1991,
Pubmed
Teitelman,
Insulin cells of pancreas extend neurites but do not arise from the neuroectoderm.
1990,
Pubmed
Waeber,
Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor.
1996,
Pubmed
Watada,
The human glucokinase gene beta-cell-type promoter: an essential role of insulin promoter factor 1/PDX-1 in its activation in HIT-T15 cells.
1996,
Pubmed
Wentworth,
Characterization of the two nonallelic genes encoding mouse preproinsulin.
1986,
Pubmed
Wessells,
Ultrastructural studies of early morphogenesis and cytodifferentiation in the embryonic mammalian pancreas.
1968,
Pubmed
Whelan,
Pancreatic beta-cell-type-specific expression of the rat insulin II gene is controlled by positive and negative cellular transcriptional elements.
1989,
Pubmed
Whelan,
Identification of a pancreatic beta-cell insulin gene transcription factor that binds to and appears to activate cell-type-specific expression: its possible relationship to other cellular factors that bind to a common insulin gene sequence.
1990,
Pubmed
de Wet,
Firefly luciferase gene: structure and expression in mammalian cells.
1987,
Pubmed
van Dijk,
extradenticle raises the DNA binding specificity of homeotic selector gene products.
1994,
Pubmed
