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Glucocorticoid receptor mediated repression of human insulin gene expression is regulated by PGC-1α

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Author(s)
Kyung-Sup KimKi-Up LeeIn-Kyu LeeWon Gu JangEun Jung KimKeun-Gyu ParkYong Bok ParkHueng-Sik ChoiHye-Jin KimYong Deuk Kim
Keimyung Author(s)
Park, Keun Gyu
Department
Dept. of Internal Medicine (내과학)
Journal Title
Biochemical and Biophysical Research Communications
Issued Date
2007
Volume
352
Issue
3
Abstract
Transcriptional regulation of the insulin gene plays a critical role in maintenance of pancreatic beta cell function in response to various stimuli. Here, we used INS-1 cells to test the hypothesis that PGC-1α regulates human insulin gene transcription by modulating glucocorticoid (GR) binding to the insulin gene promoter. Analysis of the human insulin promoter region revealed that the suppressive region regulated by GR and PGC-1α is localized from −362 to −257 bp. To locate the GR binding site in the human insulin promoter region, EMSAs were performed with candidate GR binding sequences and confirmed that a palindromic region (Palin, −284 to −274 bp) specifically interacts with GR. We also found that the Palin-binding activity of GR is increased in the presence of PGC-1α. These findings suggest that PGC-1α elevates the binding of GR to Palin and thereby enhances the GR-mediated inhibition of human insulin transcription.

Keywords
PGC-1α;
GR;
Insulin promoter;
INS-1 cells;
Palindromic region;
NRE
Keimyung Author(s)(Kor)
박근규
Publisher
School of Medicine
Citation
Kyung-Sup Kim et al. (2007). Glucocorticoid receptor mediated repression of human insulin
gene expression is regulated by PGC-1α. Biochemical and Biophysical Research Communications, 352(3), 716–721. doi: 10.1016/j.bbrc.2006.11.074
Type
Article
ISSN
0006-291X
Source
https://linkinghub.elsevier.com/retrieve/pii/S0006291X06025575
DOI
10.1016/j.bbrc.2006.11.074
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33697
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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