共查询到20条相似文献,搜索用时 15 毫秒
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Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter 总被引:18,自引:0,他引:18 下载免费PDF全文
Yoshikawa T Shimano H Amemiya-Kudo M Yahagi N Hasty AH Matsuzaka T Okazaki H Tamura Y Iizuka Y Ohashi K Osuga J Harada K Gotoda T Kimura S Ishibashi S Yamada N 《Molecular and cellular biology》2001,21(9):2991-3000
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Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c. 总被引:24,自引:0,他引:24
Guosheng Liang Jian Yang Jay D Horton Robert E Hammer Joseph L Goldstein Michael S Brown 《The Journal of biological chemistry》2002,277(11):9520-9528
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In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression 总被引:1,自引:0,他引:1
Takeuchi Y Yahagi N Nakagawa Y Matsuzaka T Shimizu R Sekiya M Iizuka Y Ohashi K Gotoda T Yamamoto M Nagai R Kadowaki T Yamada N Osuga J Shimano H 《Biochemical and biophysical research communications》2007,363(2):329-335
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Yamamoto T Shimano H Inoue N Nakagawa Y Matsuzaka T Takahashi A Yahagi N Sone H Suzuki H Toyoshima H Yamada N 《The Journal of biological chemistry》2007,282(16):11687-11695
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Deng X Yellaturu C Cagen L Wilcox HG Park EA Raghow R Elam MB 《The Journal of biological chemistry》2007,282(24):17517-17529
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Sterol regulatory element-binding proteins (SREBPs) activate genes of cholesterol and fatty acid metabolism. In each case, a ubiquitous co-regulatory factor that binds to a neighboring recognition site is also required for efficient promoter activation. It is likely that gene- and pathway-specific regulation by the separate SREBP isoforms is dependent on subtle differences in how the individual proteins function with specific co-regulators to activate gene expression. In the studies reported here we extend these observations significantly by demonstrating that SREBPs are involved in both sterol regulation and carbohydrate activation of the FAS promoter. We also demonstrate that the previously implicated Sp1 site is largely dispensable for sterol regulation in established cultured cells, whereas a CCAAT-binding factor/nuclear factor Y is critically important. In contrast, carbohydrate activation of the FAS promoter in primary hepatocytes is dependent upon SREBP and both the Sp1 and CCAAT-binding factor/nuclear factor Y sites. Because 1c is the predominant SREBP isoform expressed in hepatocytes and 1a is more abundant in sterol depleted established cell lines, this suggests that the different SREBP isoforms utilize distinct co-regulatory factors to activate target gene expression. 相似文献
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Bennett MK Seo YK Datta S Shin DJ Osborne TF 《The Journal of biological chemistry》2008,283(23):15628-15637
Mice were subjected to different dietary manipulations to selectively alter expression of hepatic sterol regulatory element-binding protein 1 (SREBP-1) or SREBP-2. mRNA levels for key target genes were measured and compared with the direct binding of SREBP-1 and -2 to the associated promoters using isoform specific antibodies in chromatin immunoprecipitation studies. A diet supplemented with Zetia (ezetimibe) and lovastatin increased and decreased nuclear SREBP-2 and SREBP-1, respectively, whereas a fasting/refeeding protocol dramatically altered SREBP-1 but had modest effects on SREBP-2 levels. Binding of both SREBP-1 and -2 increased on promoters for 3-hydroxy-3-methylglutaryl-CoA reductase, fatty-acid synthase, and squalene synthase in livers of Zetia/lovastatin-treated mice despite the decline in total SREBP-1 protein. In contrast, only SREBP-2 binding was increased for the low density lipoprotein receptor promoter. Decreased SREBP-1 binding during fasting and a dramatic increase upon refeeding indicates that the lipogenic "overshoot" for fatty-acid synthase gene expression known to occur during high carbohydrate refeeding can be attributed to a similar overshoot in SREBP-1 binding. SREBP co-regulatory protein recruitment was also increased/decreased in parallel with associated changes in SREBP binding, and there were clear distinctions for different promoters in response to the dietary manipulations. Taken together, these studies reveal that there are alternative molecular mechanisms for activating SREBP target genes in response to the different dietary challenges of Zetia/lovastatin versus fasting/refeeding. This underscores the mechanistic flexibility that has evolved at the individual gene/promoter level to maintain metabolic homeostasis in response to shifting nutritional states and environmental fluctuations. 相似文献
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A crucial role of sterol regulatory element-binding protein-1 in the regulation of lipogenic gene expression by polyunsaturated fatty acids 总被引:19,自引:0,他引:19
Yahagi N Shimano H Hasty AH Amemiya-Kudo M Okazaki H Tamura Y Iizuka Y Shionoiri F Ohashi K Osuga J Harada K Gotoda T Nagai R Ishibashi S Yamada N 《The Journal of biological chemistry》1999,274(50):35840-35844