scholarly journals c-jun inhibits transcriptional activation by the insulin enhancer, and the insulin control element is the target of control.

1994 ◽  
Vol 14 (1) ◽  
pp. 655-662 ◽  
Author(s):  
E Henderson ◽  
R Stein
Keyword(s):  
Skeletal Muscle ◽  
Beta Cells ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Pancreatic Beta Cells ◽  
Insulin Gene ◽  
Control Element ◽  
Basic Leucine Zipper ◽  
Insulin Control ◽  
Insulin Gene Transcription

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. One of the principal control elements within the enhancer is found between nucleotides -100 and -91 (GCCATCTGCT, referred to as the insulin control element [ICE]) and is regulated by both positive- and negative-acting transcription factors in the helix-loop-helix (HLH) family. It was previously shown that the c-jun proto-oncogene can repress insulin gene transcription. We have found that c-jun inhibits ICE-stimulated transcription. Inhibition of ICE-directed transcription is mediated by sequences within the carboxy-terminal region of the protein. These c-jun sequences span an activation domain and the basic leucine zipper DNA binding-dimerization region of the protein. Both regions of c-jun are conserved within the other members of the jun family: junB and junD. These proteins also suppress ICE-mediated transcription. The jun proteins do not appear to inhibit insulin gene transcription by binding directly to the ICE. c-jun and junB also block the trans-activation potential of two skeletal muscle-specific HLH proteins, MyoD and myogenin. These results suggests that the jun proteins may be common transcription control factors used in skeletal muscle and pancreatic beta cells to regulate HLH-mediated activity. We discuss the possible significance of these observations to insulin gene transcription in pancreatic beta cells.

c-jun inhibits transcriptional activation by the insulin enhancer, and the insulin control element is the target of control

1994 ◽  
Vol 14 (1) ◽  
pp. 655-662
Author(s):  
E Henderson ◽  
R Stein
Keyword(s):  
Skeletal Muscle ◽  
Beta Cells ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Pancreatic Beta Cells ◽  
Insulin Gene ◽  
Control Element ◽  
Basic Leucine Zipper ◽  
Insulin Control ◽  
Insulin Gene Transcription

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. One of the principal control elements within the enhancer is found between nucleotides -100 and -91 (GCCATCTGCT, referred to as the insulin control element [ICE]) and is regulated by both positive- and negative-acting transcription factors in the helix-loop-helix (HLH) family. It was previously shown that the c-jun proto-oncogene can repress insulin gene transcription. We have found that c-jun inhibits ICE-stimulated transcription. Inhibition of ICE-directed transcription is mediated by sequences within the carboxy-terminal region of the protein. These c-jun sequences span an activation domain and the basic leucine zipper DNA binding-dimerization region of the protein. Both regions of c-jun are conserved within the other members of the jun family: junB and junD. These proteins also suppress ICE-mediated transcription. The jun proteins do not appear to inhibit insulin gene transcription by binding directly to the ICE. c-jun and junB also block the trans-activation potential of two skeletal muscle-specific HLH proteins, MyoD and myogenin. These results suggests that the jun proteins may be common transcription control factors used in skeletal muscle and pancreatic beta cells to regulate HLH-mediated activity. We discuss the possible significance of these observations to insulin gene transcription in pancreatic beta cells.

scholarly journals Repression of insulin gene transcription by indirect genomic signaling via the estrogen receptor in pancreatic beta cells

2019 ◽  
Vol 55 (4) ◽  
pp. 226-236 ◽  
Author(s):  
Takashi Sekido ◽  
Shin-ichi Nishio ◽  
Yohsuke Ohkubo ◽  
Keiko Sekido ◽  
Junichiro Kitahara ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Beta Cells ◽  
Gene Transcription ◽  
Pancreatic Beta Cells ◽  
Insulin Gene ◽  
Insulin Gene Transcription

scholarly journals Expression of the trans-active factors that stimulate insulin control element-mediated activity appear to precede insulin gene transcription.

1994 ◽  
Vol 269 (4) ◽  
pp. 2452-2460 ◽  
Author(s):  
G.L. Robinson ◽  
M. Peshavaria ◽  
E. Henderson ◽  
S.Y. Shieh ◽  
M.J. Tsai ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Insulin Gene ◽  
Control Element ◽  
Insulin Control ◽  
Insulin Gene Transcription

scholarly journals Repression of insulin gene expression by adenovirus type 5 E1a proteins.

1987 ◽  
Vol 7 (3) ◽  
pp. 1164-1170 ◽  
Author(s):  
R W Stein ◽  
E B Ziff
Keyword(s):  
Gene Transcription ◽  
Pancreatic Beta Cells ◽  
Adenovirus Type ◽  
Insulin Gene ◽  
Mrna Levels ◽  
Beta Cell Line ◽  
Element Activity ◽  
Relationship Of ◽  
Adenovirus Type 5 ◽  
Insulin Gene Transcription

Insulin gene transcription relies on enhancer and promoter elements which are active in pancreatic beta cells. We showed that adenovirus type 5 infection of HIT T-15 cells, a transformed hamster beta cell line, represses insulin gene transcription and mRNA levels. Using expression plasmids transiently introduced into HIT T-15 cells, we showed that adenovirus type 5 E1a transcription regulatory proteins repress insulin enhancer-promoter element activity as assayed with a surrogate xanthine-guanine phosphoribosyltransferase gene. We relate E1a repression of the insulin gene to other examples of repression of enhancer-dependent genes by E1a and discuss the possible relationship of this repression to insulin gene regulation.

scholarly journals Functional characterization of the transactivation properties of the PDX-1 homeodomain protein.

1997 ◽  
Vol 17 (7) ◽  
pp. 3987-3996 ◽  
Author(s):  
M Peshavaria ◽  
E Henderson ◽  
A Sharma ◽  
C V Wright ◽  
R Stein
Keyword(s):  
Amino Acids ◽  
Gene Transcription ◽  
Transcriptional Activation ◽  
Functional Characterization ◽  
Insulin Gene ◽  
Regulatory Sequences ◽  
Homeodomain Protein ◽  
Transactivation Domain ◽  
Endogenous Insulin ◽  
Insulin Gene Transcription

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.

scholarly journals ATF3 expression is induced by low glucose in pancreatic ^|^alpha; and ^|^beta; cells and regulates glucagon but not insulin gene transcription

2014 ◽  
Vol 61 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Yong-Soo Lee ◽  
Masaki Kobayashi ◽  
Osamu Kikuchi ◽  
Tsutomu Sasaki ◽  
Hiromi Yokota-Hashimoto ◽  
...  
Keyword(s):  
Beta Cells ◽  
Gene Transcription ◽  
Insulin Gene ◽  
Low Glucose ◽  
Atf3 Expression ◽  
Insulin Gene Transcription

scholarly journals Isolation and characterization of a novel transcription factor that binds to and activates insulin control element-mediated expression.

1994 ◽  
Vol 14 (10) ◽  
pp. 6704-6714 ◽  
Author(s):  
G L Robinson ◽  
S R Cordle ◽  
E Henderson ◽  
P A Weil ◽  
G Teitelman ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Insulin Gene ◽  
Negative Regulator ◽  
Bhlh Protein ◽  
Control Element ◽  
Sequence Element ◽  
Isolation And Characterization ◽  
Insulin Control

Pancreatic beta-cell-type-specific transcription of the insulin gene is principally regulated by a single cis-acting DNA sequence element, termed the insulin control element (ICE), which is found within the 5'-flanking region of the gene. The ICE activator is a heteromeric complex composed of an islet alpha/beta-cell-specific factor associated with the ubiquitously distributed E2A-encoded proteins (E12, E47, and E2-5). We describe the isolation and characterization of a cDNA for a protein present in alpha and beta cells, termed INSAF for insulin activator factor, which binds to and activates ICE-mediated expression. INSAF was isolated from a human insulinoma cDNA library. Transfection experiments demonstrated that INSAF activates ICE expression in insulin-expressing cells but not in non-insulin-expressing cells. Cotransfection experiments showed that activation by INSAF was inhibited by Id, a negative regulator of basic helix-loop-helix (bHLH) protein function. INSAF was also shown to associate in vitro with the bHLH protein E12. In addition, affinity-purified INSAF antiserum abolished the formation of the activator-specific ICE-binding complex. Immunohistochemical studies indicate that INSAF is restricted in terms of its expression pattern, in that INSAF appears to be detected only within the nuclei of islet pancreatic alpha and beta cells. All of these data are consistent with the proposal that INSAF is either part of the ICE activator or is antigenically related to the specific activator required for insulin gene transcription.

Repression of insulin gene expression by adenovirus type 5 E1a proteins

1987 ◽  
Vol 7 (3) ◽  
pp. 1164-1170 ◽  
Author(s):  
R W Stein ◽  
E B Ziff
Keyword(s):  
Gene Transcription ◽  
Pancreatic Beta Cells ◽  
Adenovirus Type ◽  
Insulin Gene ◽  
Mrna Levels ◽  
Beta Cell Line ◽  
Element Activity ◽  
Relationship Of ◽  
Adenovirus Type 5 ◽  
Insulin Gene Transcription

Insulin gene transcription relies on enhancer and promoter elements which are active in pancreatic beta cells. We showed that adenovirus type 5 infection of HIT T-15 cells, a transformed hamster beta cell line, represses insulin gene transcription and mRNA levels. Using expression plasmids transiently introduced into HIT T-15 cells, we showed that adenovirus type 5 E1a transcription regulatory proteins repress insulin enhancer-promoter element activity as assayed with a surrogate xanthine-guanine phosphoribosyltransferase gene. We relate E1a repression of the insulin gene to other examples of repression of enhancer-dependent genes by E1a and discuss the possible relationship of this repression to insulin gene regulation.

scholarly journals c-jun inhibits insulin control element-mediated transcription by affecting the transactivation potential of the E2A gene products.

1995 ◽  
Vol 15 (3) ◽  
pp. 1398-1404 ◽  
Author(s):  
G L Robinson ◽  
E Henderson ◽  
M E Massari ◽  
C Murre ◽  
R Stein
Keyword(s):  
Amino Acids ◽  
Beta Cells ◽  
Pancreatic Beta Cell ◽  
Insulin Gene ◽  
Control Element ◽  
Transactivation Domain ◽  
Pancreatic Islet Cell ◽  
Transactivation Potential ◽  
Insulin Control

Pancreatic beta-cell-type-specific transcription of the insulin gene is principally controlled by trans-acting factors which influence insulin control element (ICE)-mediated expression. The ICE activator is composed, in part, of the basic helix-loop-helix proteins E12, E47, and E2-5 encoded by the E2A gene. Previous experiments showed that ICE activation in beta cells was repressed in vivo by the c-jun proto-oncogene (E. Henderson and R. Stein, Mol. Cell. Biol. 14:655-662, 1994). Here we focus on the mechanism by which c-Jun inhibits ICE-mediated activation. c-Jun was shown to specifically repress the transactivation potential of the E2A proteins. Thus, we found that the activity of GAL4:E2A fusion constructs was inhibited by c-Jun. The transrepression capabilities of c-Jun were detected only in pancreatic islet cell lines that contained a functional ICE activator. Repression of GAL4:E2A was mediated by the basic leucine zipper regions of c-Jun, which are also the essential regions of this protein necessary for controlling ICE activator-stimulated expression in vivo. The specific target of c-Jun repression was the transactivation domain (located between amino acids 345 and 408 in E12 and E47) conserved in E12, E47, and E2-5. In contrast, the activation domain unique to the E12 and E47 proteins (located between amino acids 1 and 99) was unresponsive to c-Jun. Our results indicate that c-Jun inhibits insulin gene transcription in beta cells by reducing the transactivation potential of the E2A proteins present in the ICE activator complex.

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