Shih S J, Allan C, Grehan S, Tse E, Moran C, Taylor J M
Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA.
J Biol Chem. 2000 Oct 13;275(41):31567-72. doi: 10.1074/jbc.M005468200.
Two distal enhancers that specify apolipoprotein (apo) E gene expression in isolated macrophages and adipose tissue were identified in transgenic mice that were generated with constructs of the human apoE/C-I/C-I'/C-IV/C-II gene cluster. One of these enhancers, multienhancer 1, consists of a 620-nucleotide sequence located 3.3 kilobases (kb) downstream of the apoE gene. The second enhancer, multienhancer 2, is a 619-nucleotide sequence located 15.9 kb downstream of the apoE gene and 5.9 kb downstream of the apoC-I gene. The two enhancers are 95% identical in sequence, and they are likely to have arisen as a consequence of the gene duplication event that yielded the apoC-I gene and the apoC-I' pseudogene. Both enhancer sequences appear to have equivalent activity in directing apoE gene expression in peritoneal macrophages and in adipocytes, suggesting that their activity in specific cell types may be determined by common regulatory elements.
在用人类载脂蛋白E/载脂蛋白C-I/载脂蛋白C-I'/载脂蛋白C-IV/载脂蛋白C-II基因簇构建体生成的转基因小鼠中，鉴定出了两个在分离的巨噬细胞和脂肪组织中特异性调控载脂蛋白（apo）E基因表达的远端增强子。其中一个增强子，即多增强子1，由位于apoE基因下游3.3千碱基（kb）处的一段620个核苷酸的序列组成。第二个增强子，多增强子2，是一段619个核苷酸的序列，位于apoE基因下游15.9 kb以及apoC-I基因下游5.9 kb处。这两个增强子的序列有95%相同，它们可能是由于产生apoC-I基因和apoC-I'假基因的基因复制事件而出现的。在指导腹膜巨噬细胞和脂肪细胞中的apoE基因表达方面，这两个增强子序列似乎具有同等活性，这表明它们在特定细胞类型中的活性可能由共同的调控元件决定。
