Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription.

摘要: Three distinct hepatocyte nuclear factor 3 (HNF-3) proteins (alpha, beta, and gamma) are known to regulate the transcription of numerous liver-specific genes. The HNF-3 bind DNA as monomers through a winged-helix motif, which is also utilized by number developmental regulators, including Drosophila homeotic fork head (fkh) protein. We have previously characterized strong-affinity HNF-3S site in transthyretin (TTR) promoter region essential for expression human hepatoma (HepG2) cells. In current study, we identify an activating protein 1 (AP-1) partially overlaps sequence TTR promoter. show that HepG2 cells AP-1 confers 12-O-tetradecanoylphorbol-13-acetate inducibility contributes normal transcriptional activity. demonstrate independently AP-1-HNF-3 site, cotransfection experiments suggest they do not cooperate activate reporter construct. addition, exposure results reciprocal decrease alpha -3 gamma may facilitate interaction with site. order explore role liver, examined patterns during acute-phase response liver regeneration. Partial hepatectomy produced minimal fluctuation expression, suggesting influenced proliferative signals induced livers, observed dramatic reduction correlates its target gene, gene. Furthermore, consistent previous studies, livers c-jun but c-fos expression. propose gene acute phase likely due lower levels induction primarily homodimers, poor activators, insufficient maintain levels. discuss reduced mediating decreased genes respond negatively cytokine signalling.