Lee S Y, Nagy B P, Brooks A R, Wang D M, Paulweber B, Levy-Wilson B
Palo Alto Medical Foundation Research Institute, California 94301, USA.
J Biol Chem. 1996 Jan 12;271(2):707-18. doi: 10.1074/jbc.271.2.707.
Apolipoprotein B (apoB) is the major protein component of low density lipoproteins, and plays a central role in cholesterol transport and metabolism. The apoB gene is transcribed in the liver and in the intestine in humans. Although much is known about the DNA sequence elements and protein factors that are important for transcription of the human apolipoprotein B gene in the liver, less is known about the mechanisms that control transcription of this gene in the intestine. The sucrose isomaltase gene (SI), is expressed exclusively in the intestine. Two sequences from the promoter region of the SI gene, namely SIF-1 and SIF-3, are essential for promoter activity of the SI gene in intestinal cells. Sequences displaying a high degree of similarity to those of SIF-1 and SIF-3 are present in the third intron of the apoB gene. Rather than stimulating apoB promoter activity, the BSIF-1 and BSIF-3 sequences repressed transcription in CaCo-2 cells. Gel retardation studies demonstrated that BSIF-1, like SIF-1, binds to proteins related to the caudal family of proteins such as mCdx-4 and mCdx-2. These proteins appear to repress transcription from the apoB promoter by a mechanism that involves an interaction with members of the C/EBP family of proteins, that bind to a target sequence for the repressor in the segment from -139 to -111 of the apoB promoter. On the other hand, BSIF-3, like SIF-3, binds to HNF-1 and also represses transcription from the apoB promoter.
载脂蛋白B（apoB）是低密度脂蛋白的主要蛋白质成分，在胆固醇运输和代谢中起核心作用。apoB基因在人类的肝脏和肠道中进行转录。尽管对于肝脏中人类载脂蛋白B基因转录重要的DNA序列元件和蛋白质因子已了解很多，但对于该基因在肠道中转录的调控机制却知之甚少。蔗糖异麦芽糖酶基因（SI）仅在肠道中表达。SI基因启动子区域的两个序列，即SIF-1和SIF-3，对于SI基因在肠道细胞中的启动子活性至关重要。在apoB基因的第三个内含子中存在与SIF-1和SIF-3高度相似的序列。与刺激apoB启动子活性不同，BSIF-1和BSIF-3序列在CaCo-2细胞中抑制转录。凝胶阻滞研究表明，BSIF-1与SIF-1一样，能与尾蛋白家族相关的蛋白质如mCdx-4和mCdx-2结合。这些蛋白质似乎通过一种机制抑制apoB启动子的转录，该机制涉及与C/EBP蛋白质家族成员的相互作用，这些成员结合到apoB启动子-139至-111区域中阻遏物的靶序列上。另一方面，BSIF-3与SIF-3一样，能与肝细胞核因子-1（HNF-1）结合，也抑制apoB启动子的转录。
