scholarly journals Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs

2006 ◽  
Vol 400 (1) ◽  
pp. 179-188 ◽  
Author(s):  
Nicolas Dif ◽  
Vanessa Euthine ◽  
Estelle Gonnet ◽  
Martine Laville ◽  
Hubert Vidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Regulatory Element ◽  
Expression Vectors ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Direct Role ◽  
Human Skeletal Muscle Cells ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

In the present study, we aimed to decipher the mechanisms involved in the transcriptional effect of insulin on the SREBP-1c specific promoter of the human srebf-1 gene. Using luciferase reporter gene constructs in HEK-293 cells (human embryonic kidney cells), we demonstrated that the full effect of insulin requires the presence of SREs (sterol response elements) in the proximal region of the promoter. Furthermore, insulin increases the binding of SREBP-1 (sterol-regulatory-element-binding protein-1) to this promoter region in chromatin immunoprecipitation assay. We also found that the nuclear receptors LXRs (liver X receptors) strongly activate SREBP-1c gene expression and identified the LXRE (LXR-response element) involved in this effect. However, our results suggested that these LXREs do not play a major role in the response to insulin. Finally, using expression vectors and adenoviruses allowing ectopic overexpressions of the human mature forms of SREBP-1a or SREBP-1c, we demonstrated the direct role of SREBP-1 in the control of SREBP-1c gene expression in human skeletal-muscle cells. Altogether, these results strongly suggest that the SREBP-1 transcription factors are the main mediators of insulin action on SREBP-1c expression in human tissues.

scholarly journals Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c) promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis-acting elements

2004 ◽  
Vol 385 (1) ◽  
pp. 207-216 ◽  
Author(s):  
Lauren M. CAGEN ◽  
Xiong DENG ◽  
Henry G. WILCOX ◽  
Edwards A. PARK ◽  
Rajendra RAGHOW ◽  
...  
Keyword(s):  
Binding Protein ◽  
Regulatory Element ◽  
Ectopic Expression ◽  
Rat Hepatocytes ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Cis Acting ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

The enhanced synthesis of fatty acids in the liver and adipose tissue in response to insulin is critically dependent on the transcription factor SREBP-1c (sterol-regulatory-element-binding protein 1c). Insulin increases the expression of the SREBP-1c gene in intact liver and in hepatocytes cultured in vitro. To learn the mechanism of this stimulation, we analysed the activation of the rat SREBP-1c promoter and its truncated or mutated congeners driving a luciferase reporter gene in transiently transfected rat hepatocytes. The rat SREBP-1c promoter contains binding sites for LXR (liver X receptor), Sp1, NF-Y (nuclear factor-Y) and SREBP itself. We have found that each of these sites is required for the full stimulatory response of the SREBP-1c promoter to insulin. Mutation of either the putative LXREs (LXR response elements) or the SRE (sterol response element) in the proximal SREBP-1c promoter reduced the stimulatory effect of insulin by about 50%. Insulin and the LXR agonist TO901317 increased the association of SREBP-1 with the SREBP-1c promoter. Ectopic expression of LXRα or SREBP-1c increased activity of the SREBP-1c promoter, and this effect is further enhanced by insulin. The Sp1 and NF-Y sites adjacent to the SRE are also required for full activation of the SREBP-1c promoter by insulin. We propose that the combined actions of the SRE, LXREs, Sp1 and NF-Y elements constitute an insulin-responsive cis-acting unit of the SREBP-1c gene in the liver.

scholarly journals Sterol Regulatory Element-binding Protein-2- and Liver X Receptor-driven Dual Promoter Regulation of Hepatic ABC Transporter A1 Gene Expression

2007 ◽  
Vol 282 (29) ◽  
pp. 21090-21099 ◽  
Author(s):  
Norimasa Tamehiro ◽  
Yukari Shigemoto-Mogami ◽  
Tomoshi Kakeya ◽  
Kei-ichiro Okuhira ◽  
Kazuhiro Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Abc Transporter ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Promoter Regulation ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Dual Promoter

scholarly journals Transcription Factor Sterol Regulatory Element Binding Protein 2 Regulates Scavenger Receptor Cla-1 Gene Expression

2004 ◽  
Vol 24 (12) ◽  
pp. 2358-2364 ◽  
Author(s):  
Morgan Tréguier ◽  
Chantal Doucet ◽  
Martine Moreau ◽  
Christiane Dachet ◽  
Joëlle Thillet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Protein ◽  
Regulatory Element ◽  
Scavenger Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

2015 ◽  
Vol 35 (2) ◽  
pp. 803-815 ◽  
Author(s):  
Andreas Bitter ◽  
Andreas K. Nüssler ◽  
Wolfgang E. Thasler ◽  
Kathrin Klein ◽  
Ulrich M. Zanger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipogenic Gene ◽  
Knock Down ◽  
Lipogenic Gene Expression ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

scholarly journals FoxO1 Inhibits Sterol Regulatory Element-binding Protein-1c (SREBP-1c) Gene Expression via Transcription Factors Sp1 and SREBP-1c

2012 ◽  
Vol 287 (24) ◽  
pp. 20132-20143 ◽  
Author(s):  
Xiong Deng ◽  
Wenwei Zhang ◽  
InSug O-Sullivan ◽  
J. Bradley Williams ◽  
Qingming Dong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Abstract 148: Sterol Regulatory Element-Binding Protein-1 Is Involved in the Development of Angiotensin II-Induced Cardiac Fibrosis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Satoshi Sakai ◽  
Yoshimi Nakagawa ◽  
Nobutake Shimojo ◽  
Taizo Kimura ◽  
Kazuko Tajiri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Angiotensin Ii ◽  
Cardiac Dysfunction ◽  
Cardiac Fibrosis ◽  
Binding Protein ◽  
Regulatory Element ◽  
Antioxidant Genes ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Sterol Regulatory Element Binding Protein (SREBP)-1 is a transcription factor for triglyceride synthesis. SREBP-1 is shown to contribute to the organ damages such as pancreatic beta cell, liver, and kidney; however, it is unclear whether SREBP-1 also contributes to the cardiac pathogenesis. We made cardiac dysfunction and fibrosis model by 2-week infusion of angiotensin II (A-II, 1.44 mg/kg BW/day). Mice were divided into followings (n=5∼6 in each group): wild with vehicle (WC), wild with A-II (WA), SREBP-1 knockout mice (SREBP-KO) with vehicle (SC), and SREBP-KO with A-II (SA). WA clearly demonstrated cardiac dysfunction and severe perivascular fibrosis compared to WC; however, these findings were not observed in SA compared to SC. We analyzed gene expression by DNA microarray using the software DAVID and quantitative RT-PCR to find gene clusters mostly illustrative for these phenotypes. Gene expression of extracellular matrix (Col1a, 3a, periostin) was increased in WA. Highly scored annotations in WA were chemokines (CCL5, CXCL10) and their receptors (CCR5, CXCR3), and Th2 cytokines (IL-13 and TGFb), suggesting that chronic inflammatory and repairing responses occurred. These changes were normalized in SA compared to SC. Expression of NOX4, a component of NADPH oxidase, was significantly increased in WA and SA compared to each control in a similar extent, suggesting that the Ang II-induced oxidative stress to the heart did not differ. To elucidate why the cardiac fibrosis differed between WA and SA, we analyzed the expression of transcription factors. Nrf2, a transcription factor for detoxification and anti-oxidant gene against to reactive oxygen species (ROS), was significantly decreased in WA compared to WC; however, it did not differ between in SA and SC. Furthermore, expression of the Nrf2-inducible genes HO-1 and NQO1, antioxidant genes, was significantly decreased in WA compared to WC; meanwhile, there were no differences between in SA and SC. [Conclusion] SREBP-1 may positively contribute to the A-II-induced cardiac fibrosis via the involvement of chronic inflammatory responses, which is induced partly by the reduction of antioxidant activity.

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