共查询到20条相似文献,搜索用时 15 毫秒
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Prieur X Schaap FG Coste H Rodríguez JC 《Molecular endocrinology (Baltimore, Md.)》2005,19(12):3107-3125
The recently discovered apolipoprotein AV (apoAV) gene has been reported to be a key player in modulating plasma triglyceride levels. Here we identify the hepatocyte nuclear factor-4alpha (HNF-4alpha) as a novel regulator of human apoAV gene. Inhibition of HNF-4alpha expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4alpha directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4alpha consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha was capable of stimulating the HNF-4alpha-dependent transactivation of apoAV promoter. Furthermore, analyses in human hepatic cells demonstrated that AMP-activated protein kinase (AMPK) and the MAPK signaling pathway regulate human apoAV expression and suggested that this regulation may be mediated, at least in part, by changes in HNF-4alpha. Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4alpha gene revealed a species-distinct regulation of apoAV by HNF-4alpha, which resembles that of a subset of HNF-4alpha target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4alpha and underscore the role of HNF-4alpha in regulating triglyceride metabolism. 相似文献
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An alternative, human SRC promoter and its regulation by hepatic nuclear factor-1alpha 总被引:2,自引:0,他引:2
Bonham K Ritchie SA Dehm SM Snyder K Boyd FM 《The Journal of biological chemistry》2000,275(48):37604-37611
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Geier A Martin IV Dietrich CG Balasubramaniyan N Strauch S Suchy FJ Gartung C Trautwein C Ananthanarayanan M 《American journal of physiology. Gastrointestinal and liver physiology》2008,295(2):G226-G233
Sodium taurocholate cotransporting polypeptide (Ntcp) is the major uptake system for conjugated bile acids. Deletions of hepatocyte nuclear factor (HNF)-1alpha and retinoid X receptor-alpha:retinoic acid receptor-alpha binding sites in the mouse 5'-flanking region corresponding to putatively central regulatory elements of rat Ntcp do not significantly reduce promoter activity. We hypothesized that HNF-4alpha, which is increasingly recognized as a central regulator of hepatocyte function, may directly transactivate mouse (mNtcp). A 1.1-kb 5'-upstream region including the mouse Ntcp promoter was cloned and compared with the rat promoter. In contrast to a moderate 3.5-fold activation of mNtcp by HNF-1alpha, HNF-4alpha cotransfection led to a robust 20-fold activation. Deletion analysis of mouse and rat Ntcp promoters mapped a conserved HNF-4alpha consensus site at -345/-326 and -335/-316 bp, respectively. p-475bpmNtcpLUC is not transactivated by HNF-1alpha but shows a 50-fold enhanced activity upon cotransfection with HNF-4alpha. Gel mobility shift assays demonstrated a complex of the HNF-4alpha-element formed with liver nuclear extracts that was blocked by an HNF-4alpha specific antibody. HNF-4alpha binding was confirmed by chromatin immunoprecipitation. Using Hepa 1-6 cells, HNF-4alpha-knockdown resulted in a significant 95% reduction in NTCP mRNA. In conclusion, mouse Ntcp is regulated by HNF-4alpha via a conserved distal cis-element independently of HNF-1alpha. 相似文献
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Tarumi T Kravtsov DV Zhao M Williams SM Gailani D 《The Journal of biological chemistry》2002,277(21):18510-18516
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Boudreau F Rings EH van Wering HM Kim RK Swain GP Krasinski SD Moffett J Grand RJ Suh ER Traber PG 《The Journal of biological chemistry》2002,277(35):31909-31917
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SREBP-1 interacts with hepatocyte nuclear factor-4 alpha and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes 总被引:12,自引:0,他引:12
Yamamoto T Shimano H Nakagawa Y Ide T Yahagi N Matsuzaka T Nakakuki M Takahashi A Suzuki H Sone H Toyoshima H Sato R Yamada N 《The Journal of biological chemistry》2004,279(13):12027-12035
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