scholarly journals Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

Diabetologia ◽  
2008 ◽  
Vol 51 (8) ◽  
pp. 1429-1439 ◽  
Author(s):  
D. Martin ◽  
F. Allagnat ◽  
G. Chaffard ◽  
D. Caille ◽  
M. Fukuda ◽  
...  
2004 ◽  
Vol 101 (28) ◽  
pp. 10458-10463 ◽  
Author(s):  
A. W. Bruce ◽  
I. J. Donaldson ◽  
I. C. Wood ◽  
S. A. Yerbury ◽  
M. I. Sadowski ◽  
...  

2003 ◽  
Vol 334 (5) ◽  
pp. 863-874 ◽  
Author(s):  
Ian C. Wood ◽  
Nikolai D. Belyaev ◽  
Alexander W. Bruce ◽  
Caroline Jones ◽  
Mohini Mistry ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e31062 ◽  
Author(s):  
Fabrice Moore ◽  
Izortze Santin ◽  
Tatiane C. Nogueira ◽  
Esteban N. Gurzov ◽  
Lorella Marselli ◽  
...  

2014 ◽  
Author(s):  
Chunyu Bai ◽  
Xiangchen Li ◽  
Yuhua Gao ◽  
Taofeng Lu ◽  
Kunfu Wang ◽  
...  

MicroRNAs (miRNAs) are small noncoding RNAs that bind to the 3?-UTR of mRNAs and function mainly in post-transcriptional regulation. MiRNAs have been implicated to play roles in organ development, including that of the pancreas. Many miRNAs, such as miR-375, miR-124, miR-7, miR-21 and miR-221, have been shown to regulate insulin production as well as insulin secretion. However, it is not known whether miRNAs can regulate insulin secretion via the control of intracellular Ca2+ in pancreatic beta cells. In this research, expression profiles of miRNAs and mRNAs were investigated using RNA-sequencing and microarray analysis in chicken pancreatic nestin-positive progenitor cells and differentiated pancreatic beta cells. A number of miRNAs were up-regulated after differentiation of progenitors into beta cells, which regulate cell signaling pathways to control cell function. miR-223 and miR146a were shown to promote insulin secretion from pancreatic beta cells by regulating the concentration of intracellular Ca2+ via the down-regulation of their target genes.


2013 ◽  
Vol 110 (40) ◽  
pp. 15997-16002 ◽  
Author(s):  
X. Wang ◽  
L. Jiang ◽  
O. Wallerman ◽  
U. Engstrom ◽  
A. Ameur ◽  
...  

2008 ◽  
Vol 28 (14) ◽  
pp. 4588-4597 ◽  
Author(s):  
Anaïs Perilhou ◽  
Cécile Tourrel-Cuzin ◽  
Pili Zhang ◽  
Ilham Kharroubi ◽  
Haiyan Wang ◽  
...  

ABSTRACT Pancreatic islet beta cell differentiation and function are dependent upon a group of transcription factors that maintain the expression of key genes and suppress others. Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4α (HNF4α) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. Here, we demonstrate specific HNF4α activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. The stable association of the endogenous HNF4α with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. Mutation experiments showed that this DR-1 site is essential for HNF4α transactivation of COUP-TFII. The dominant negative suppression of HNF4α function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4α mRNA levels in 832/13 INS-1 cells to decrease. This positive regulation of HNF4α by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4α mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4α/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells.


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