Chuang S S, Zhuang H, Reisher S R, Feinstein S I, Das H K
Department of Pharmacology, University of North Texas, Fort Worth 76107, USA.
Biochem Biophys Res Commun. 1995 Oct 4;215(1):394-404. doi: 10.1006/bbrc.1995.2478.
Apolipoprotein B-100, produced primarily in the human liver, is the sole protein component of low-density lipoprotein and serves as a ligand for the LDL receptor. Two cis-acting positive elements between -128 and -70 control hepatic cell-specific expression of the human apoB gene (H. K. Das, T. Leff, and J. L. Breslow, J. Biol. Chem. 263: 11452-11458, 1988). In this study, two apoB cis-acting elements (+20 to +40; +43 to +53) have been identified using DNase I footprint analysis. Through in vitro mutagenesis and transient transfection experiments in Hep G2 and HeLa cells, the element (+20 to +40) was observed to have a negative effect on transcription of the apoB gene. The element (+43 to +53) was found to have a strong positive effect on apoB gene transcription in Hep G2 cells and mild positive effect in HeLa cells. Therefore these two cis-acting elements mediate hepatic-cell specific expression of the apolipoprotein gene by interacting with trans-acting protein factors.
载脂蛋白B - 100主要在人类肝脏中产生，是低密度脂蛋白的唯一蛋白质成分，并作为低密度脂蛋白受体的配体。在 - 128和 - 70之间的两个顺式作用阳性元件控制着人类载脂蛋白B基因的肝细胞特异性表达（H. K. 达斯、T. 莱夫和J. L. 布雷斯洛，《生物化学杂志》263: 11452 - 11458，1988年）。在本研究中，已使用DNase I足迹分析鉴定出两个载脂蛋白B顺式作用元件（+20至 +40；+43至 +53）。通过在Hep G2和HeLa细胞中的体外诱变和瞬时转染实验，观察到元件（+20至 +40）对载脂蛋白B基因的转录有负面影响。发现元件（+43至 +53）对Hep G2细胞中载脂蛋白B基因转录有强烈的正向作用，而在HeLa细胞中有轻微的正向作用。因此，这两个顺式作用元件通过与反式作用蛋白因子相互作用来介导载脂蛋白基因的肝细胞特异性表达。
