Allan C M, Walker D, Taylor J M
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100, USA.
J Biol Chem. 1995 Nov 3;270(44):26278-81. doi: 10.1074/jbc.270.44.26278.
We have identified a second hepatic control region (HCR-2) in the human apolipoprotein (apo) E gene locus that confers liver expression of the human apoE gene in transgenic mice. This HCR-2 sequence is located 27 kilobases downstream of the apoE gene and 10 kilobases downstream of the previously described liver-specific enhancer (HCR-1). Nucleotide sequence analysis of the HCR-2 region revealed a sequence that shares 85% identity to the functional 319-base pair domain of HCR-1. To test its activity, transgenic mice were prepared with a fusion construct containing a human apoE gene fragment, which is not normally expressed in the liver, ligated to a 632-base pair region containing the HCR-2 sequence. This construct resulted in high levels of liver-specific apoE transgene expression, indicating that HCR-2 can function as a hepatic enhancer and has an activity similar to that of HCR-1. Hence, these findings suggest that there are at least two hepatic control regions, HCR-1 and HCR-2, capable of controlling the liver expression of this human apolipoprotein gene locus.
我们在人类载脂蛋白（apo）E基因座中鉴定出了第二个肝脏控制区域（HCR-2），该区域可在转基因小鼠中赋予人类apoE基因肝脏表达。这个HCR-2序列位于apoE基因下游27千碱基处，以及先前描述的肝脏特异性增强子（HCR-1）下游10千碱基处。对HCR-2区域的核苷酸序列分析显示，该序列与HCR-1的功能性319碱基对结构域有85%的同一性。为了测试其活性，制备了转基因小鼠，其携带一个融合构建体，该构建体包含一个在肝脏中通常不表达的人类apoE基因片段，与一个包含HCR-2序列的632碱基对区域相连。这个构建体导致了高水平的肝脏特异性apoE转基因表达，表明HCR-2可以作为肝脏增强子发挥作用，并且具有与HCR-1相似的活性。因此，这些发现表明，至少有两个肝脏控制区域，即HCR-1和HCR-2，能够控制这个人类载脂蛋白基因座的肝脏表达。
