To access the full text documents, please follow this link:

Hepatocyte nuclear factor-4 alpha regulates the human apolipoprotein AV gene: Identification of a novel response element and involvement in the control by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, AMP-activated protein kinase, and mitogen-activated protein kinase pathway
Prieur, Xavier; Schaap, Frank G.; Coste, Hervé; Rodríguez Rubio, Joan Carles
Universitat de Barcelona
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-4 (HNF-4 ) as a novel regulator of human apoAV gene. Inhibition of HNF-4 expression by small interfering RNA resulted in down-regulation of apoAV. Deletion, mutagenesis, and binding assays revealed that HNF-4 directly regulates human apoAV promoter through DR1 [a direct repeat separated by one nucleotide (nt)], and via a novel element for HNF-4 consisting of an inverted repeat separated by 8 nt (IR8). In addition, we show that the coactivator peroxisome proliferator-activated receptor- coactivator-1 was capable of stimulating the HNF-4 -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-4 . Intriguingly, EMSAs and mice with a liver-specific disruption of the HNF-4 gene revealed a species-distinct regulation of apoAV by HNF-4 , which resembles that of a subset of HNF-4 target genes. Taken together, our data provide new insights into the binding properties and the modulation of HNF-4 and underscore the role of HNF-4 in regulating triglyceride metabolism.
Receptors nuclears (Bioquímica)
Factors de transcripció
Àcids nucleics
Nuclear receptors (Biochemistry)
Transcription factors
Nucleic acids
(c) Endocrine Society, 2005
Endocrine Society

Show full item record

Related documents

Other documents of the same author

Prieur, Xavier; Huby, Thierry; Coste, Hervé; Schaap, Frank G.; Chapman, M. John; Rodríguez Rubio, Joan Carles
Prieur, Xavier; Lesnik, Philipp; Moreau, Martine; Rodríguez Rubio, Joan Carles; Doucet, Chantal; Chapman, M. John; Huby, Thierry
Langhi, Cédric; Pedraz Cuesta, Elena; Donate, Yolanda; Marrero González, Pedro F.; Haro Bautista, Diego; Rodríguez Rubio, Joan Carles