Duplicated downstream enhancers control expression of the human apolipoprotein E gene in macrophages and adipose tissue
Duplicated downstream enhancers control expression of the human apolipoprotein E gene in macrophages and adipose tissue
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DOI：
10.1074/jbc.m005468200
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发表时间：
2000-10-13
影响因子：
4.8
通讯作者：
Taylor, JM
中科院分区：
文献类型：
--
作者：
Shih, SJ;Allan, C;Taylor, JM
在用人 apoE/C-I/C-I'/C-IV/C-II 基因簇构建体生成的转基因小鼠中，鉴定了在分离的巨噬细胞和脂肪组织中指定载脂蛋白 (apo) E 基因表达的两个远端增强子。这些增强子之一，即多增强子 1，由位于 apoE 基因下游 3.3 KB 处的 620 个核苷酸序列组成。第二个增强子，多增强子 2，是一个 619 个核苷酸的序列，位于 apoE 基因下游 15.9 kb 和 apoC-I 基因下游 5.9 kb。这两个增强子的序列有 95% 相同，并且它们很可能是由于产生 apoC-I 基因和 apoC-I' 假基因的基因复制事件而产生的。两种增强子序列似乎在指导腹膜巨噬细胞和脂肪细胞中 apoE 基因表达方面具有相同的活性，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。
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.