Insulin Gene Transcription: Factors Involved in Cell Type-Specific and Glucose-Regulated Expression in Islet β Cells are Also Essential During Pancreatic Development

2011 ◽  
Author(s):  
Roland Stein
Keyword(s):  
Transcription Factors ◽  
Gene Transcription ◽  
Insulin Gene ◽  
Cell Type ◽  
Β Cells ◽  
Pancreatic Development ◽  
Regulated Expression ◽  
Cell Type Specific ◽  
Insulin Gene Transcription

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.

Short-term regulation of insulin gene transcription

2002 ◽  
Vol 30 (2) ◽  
pp. 312-317 ◽  
Author(s):  
B. Leibiger ◽  
T. Moede ◽  
S. Uhles ◽  
P.-O. Berggren ◽  
I. B. Leibiger
Keyword(s):  
Insulin Secretion ◽  
Gene Transcription ◽  
Insulin Gene ◽  
Current View ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Short Term ◽  
Major Nutrient ◽  
Glucose Metabolites ◽  
Insulin Gene Transcription

Short-term regulation of insulin gene transcription is still a matter of debate. However, an increasing body of evidence shows that insulin gene transcription is affected by signals, such as incretins, glucose metabolites, intracellular Ca2+, and by insulin secreted from pancreatic β-cells, all supporting the concept of an immediate response resulting in insulin gene transcription following food-uptake. The present review aims to summarize the current view on the mechanisms underlying the up-regulation of insulin gene transcription in response to glucose, the major nutrient factor in insulin secretion and biosynthesis.

scholarly journals Regulation of Insulin Gene Transcription by ERK1 and ERK2 in Pancreatic β Cells

2003 ◽  
Vol 278 (35) ◽  
pp. 32969-32977 ◽  
Author(s):  
Shih Khoo ◽  
Steven C. Griffen ◽  
Ying Xia ◽  
Richard J. Baer ◽  
Michael S. German ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Insulin Gene Transcription

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 Transcription Is Mediated by Interactions between the p300 Coactivator and PDX-1, BETA2, and E47

2002 ◽  
Vol 22 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Yi Qiu ◽  
Min Guo ◽  
Suming Huang ◽  
Roland Stein
Keyword(s):  
Dna Binding ◽  
Rna Polymerase Ii ◽  
Gene Transcription ◽  
Present Report ◽  
Amino Acid Sequences ◽  
Insulin Gene ◽  
Homeodomain Protein ◽  
Β Cells ◽  
Β Cell ◽  
Insulin Gene Transcription

ABSTRACT Pancreatic β-cell-type-specific expression of the insulin gene requires both ubiquitous and cell-enriched activators, which are organized within the enhancer region into a network of protein-protein and protein-DNA interactions to promote transcriptional synergy. Protein-protein-mediated communication between DNA-bound activators and the RNA polymerase II transcriptional machinery is inhibited by the adenovirus E1A protein as a result of E1A’s binding to the p300 coactivator. E1A disrupts signaling between the non-DNA-binding p300 protein and the basic helix-loop-helix DNA-binding factors of insulin’s E-element activator (i.e., the islet-enriched BETA2 and generally distributed E47 proteins), as well as a distinct but unidentified enhancer factor. In the present report, we show that E1A binding to p300 prevents activation by insulin’s β-cell-enriched PDX-1 activator. p300 interacts directly with the N-terminal region of the PDX-1 homeodomain protein, which contains conserved amino acid sequences essential for activation. The unique combination of PDX-1, BETA2, E47, and p300 was shown to promote synergistic activation from a transfected insulin enhancer-driven reporter construct in non-β cells, a process inhibited by E1A. In addition, E1A inhibited the level of PDX-1 and BETA2 complex formation in β cells. These results indicate that E1A inhibits insulin gene transcription by preventing communication between the p300 coactivator and key DNA-bound activators, like PDX-1 and BETA2:E47.

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 Covalent Histone Modifications Underlie the Developmental Regulation of Insulin Gene Transcription in Pancreatic β Cells

2003 ◽  
Vol 278 (26) ◽  
pp. 23617-23623 ◽  
Author(s):  
Swarup K. Chakrabarti ◽  
Joshua Francis ◽  
Suzanne M. Ziesmann ◽  
James C. Garmey ◽  
Raghavendra G. Mirmira
Keyword(s):  
Gene Transcription ◽  
Histone Modifications ◽  
Developmental Regulation ◽  
Insulin Gene ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Covalent Histone Modifications ◽  
Insulin Gene Transcription
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