|Expression of the Human Glucokinase Gene: Important Roles of the 5 ′ Flanking and Intron 1 Sequences|
|Wang, Yi1; Guo, Tingting1; Zhao, Shuyong1; Li, Zhixin1; Mao, Yiqing1; Li, Hui1; Wang, Xi1; Wang, Rong1; Xu, Wei1; Song, Rongjing1; Jin, Ling1; Li, Xiuli2; Irwin, David M.1,3; Niu, Gang4; Tan, Huanran1|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Science & Technology - Other Topics|
|关键词[WOS]||I-HYPERSENSITIVE SITES ; ELEMENT-BINDING PROTEIN-1C ; GENOMIC DNA-SEQUENCES ; MAMMALIAN GLUCOKINASE ; PRIMARY HEPATOCYTES ; LIVER ; INSULIN ; IDENTIFICATION ; TRANSCRIPTION ; INDUCTION|
Background: Glucokinase plays important tissue-specific roles in human physiology, where it acts as a sensor of blood glucose levels in the pancreas, and a few other cells of the gut and brain, and as the rate-limiting step in glucose metabolism in the liver. Liver-specific expression is driven by one of the two tissue-specific promoters, and has an absolute requirement for insulin. The sequences that mediate regulation by insulin are incompletely understood.
Methodology/Principal Findings: To better understand the liver-specific expression of the human glucokinase gene we compared the structures of this gene from diverse mammals. Much of the sequence located between the 5′ pancreatic beta-cell-specific and downstream liver-specific promoters of the glucokinase genes is composed of repetitive DNA elements that were inserted in parallel on different mammalian lineages. The transcriptional activity of the liver-specific promoter 5′ flanking sequences were tested with and without downstream intronic sequences in two human liver cells lines, HepG2 and L-02. While glucokinase liver-specific 5′ flanking sequences support expression in liver cell lines, a sequence located about 2000 bases 3′ to the liver-specific mRNA start site represses gene expression. Enhanced reporter gene expression was observed in both cell lines when cells were treated with fetal calf serum, but only in the L-02 cells was expression enhanced by insulin.
Conclusions/Significance: Our results suggest that the normal liver L-02 cell line may be a better model to understand the regulation of the liver-specific expression of the human glucokinase gene. Our results also suggest that sequences downstream of the liver-specific mRNA start site have important roles in the regulation of liver-specific glucokinase gene expression.
|作者单位||1.Chifeng Coll, Dept Pharmacol, Chifeng, Peoples R China|
2.Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
3.Beijing N&N Genetech Co, Beijing, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Pharmacol, Beijing 100871, Peoples R China
|Wang, Yi,Guo, Tingting,Zhao, Shuyong,et al. Expression of the Human Glucokinase Gene: Important Roles of the 5 ′ Flanking and Intron 1 Sequences[J]. PLOS ONE,2012,7(9).|
|APA||Wang, Yi.,Guo, Tingting.,Zhao, Shuyong.,Li, Zhixin.,Mao, Yiqing.,...&Tan, Huanran.(2012).Expression of the Human Glucokinase Gene: Important Roles of the 5 ′ Flanking and Intron 1 Sequences.PLOS ONE,7(9).|
|MLA||Wang, Yi,et al."Expression of the Human Glucokinase Gene: Important Roles of the 5 ′ Flanking and Intron 1 Sequences".PLOS ONE 7.9(2012).|