Insulin gene enhancer activity is inhibited by adenovirus 5 E1a gene products

1989 ◽  
Vol 9 (10) ◽  
pp. 4531-4534
Author(s):  
R W Stein ◽  
J Whelan
Keyword(s):  
Transcription Factors ◽  
Gene Transcription ◽  
Dna Sequences ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Insulin Gene ◽  
Target Sequence ◽  
Flanking Region ◽  
Cellular Transcription ◽  
Insulin Gene Transcription

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located within the 5'-flanking region of the insulin gene. Transcription from the enhancer is controlled by both positive- and negative-acting cellular transcription factors. It was previously shown that both the 243- and 289-amino-acid adenovirus type 5 E1a proteins can repress insulin gene transcription in vivo. To localize the insulin DNA sequences involved in this response, we examined the effects of a number of mutations within the 5'-flanking region of the rat insulin II gene on E1a-mediated repression of insulin gene transcription. We have found that E1a proteins inhibit enhancer-stimulated transcription of the insulin gene. The enhancer appears to contain at least two genetically separable and independent E1a target sequence elements. Interestingly, these same regions of the insulin enhancer have been shown to be negatively regulated by cellular transcription factors. These results suggest that E1a-like cellular factors may function in the pancreatic beta-cell-specific expression of the insulin gene.

scholarly journals Insulin gene enhancer activity is inhibited by adenovirus 5 E1a gene products.

1989 ◽  
Vol 9 (10) ◽  
pp. 4531-4534 ◽  
Author(s):  
R W Stein ◽  
J Whelan
Keyword(s):  
Transcription Factors ◽  
Gene Transcription ◽  
Dna Sequences ◽  
Pancreatic Beta Cells ◽  
Pancreatic Beta Cell ◽  
Insulin Gene ◽  
Target Sequence ◽  
Flanking Region ◽  
Cellular Transcription ◽  
Insulin Gene Transcription

Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located within the 5'-flanking region of the insulin gene. Transcription from the enhancer is controlled by both positive- and negative-acting cellular transcription factors. It was previously shown that both the 243- and 289-amino-acid adenovirus type 5 E1a proteins can repress insulin gene transcription in vivo. To localize the insulin DNA sequences involved in this response, we examined the effects of a number of mutations within the 5'-flanking region of the rat insulin II gene on E1a-mediated repression of insulin gene transcription. We have found that E1a proteins inhibit enhancer-stimulated transcription of the insulin gene. The enhancer appears to contain at least two genetically separable and independent E1a target sequence elements. Interestingly, these same regions of the insulin enhancer have been shown to be negatively regulated by cellular transcription factors. These results suggest that E1a-like cellular factors may function in the pancreatic beta-cell-specific expression of the insulin gene.

scholarly journals PIASy is a SUMOylation-independent negative regulator of the insulin transactivator MafA

2019 ◽  
Vol 63 (4) ◽  
pp. 297-308
Author(s):  
Suzuka Onishi ◽  
Kohsuke Kataoka
Keyword(s):  
Transcription Factors ◽  
Gene Transcription ◽  
Gene Promoter ◽  
Terminal Region ◽  
Insulin Gene ◽  
Negative Regulator ◽  
Β Cell ◽  
E3 Ligases ◽  
Amino Terminal ◽  
Insulin Gene Transcription

Insulin plays a central role in glucose homeostasis and is produced exclusively by pancreatic islet β-cells. Insulin gene transcription is regulated by a set of β-cell-enriched transcription factors that bind to cis-regulatory elements within the promoter region, and regulation of the insulin gene promoter is closely linked to β-cell functionality. PIASy, a member of the PIAS family of SUMO E3 ligases, is thought to affect insulin gene transcription, but its mechanism of action is not fully understood. Here, we demonstrate that PIASy interacts with MafA and represses insulin gene promoter activity. MafA is a β-cell-restricted basic leucine-zipper transcriptional activator that binds to the C1 element of the insulin gene promoter. In line with previous studies showing the transactivator domain of MafA is SUMOylated, PIASy enhanced the SUMOylation of MafA. However, a SUMOylation-deficient mutant of MafA was still repressed by PIASy, indicating that this modification is dispensable for repression. Using a series of MafA and PIASy mutants, we found that the basic domain of MafA and the amino-terminal region of PIASy containing the SAP domain are necessary for their interaction. In addition, SUMO-interacting motif 1 (SIM1) at the carboxyl-terminal region of PIASy was required to repress the synergistic transactivation of MafA, Pdx1, and Beta2, transcription factors playing central roles in β-cell differentiation and function. The PINIT and SP-RING domains in the middle region of PIASy were dispensable. These findings suggest that PIASy binds to MafA through the SAP domain and negatively regulates the insulin gene promoter through a novel SIM1-dependent mechanism.

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.

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.

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 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
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