Feuchter A, Mager D
Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, Canada.
Nucleic Acids Res. 1990 Mar 11;18(5):1261-70. doi: 10.1093/nar/18.5.1261.
The human genome contains a variety of elements similar in structure to retroviruses and retrotransposons. We have shown that the long terminal repeat (LTR) sequences of a large family of human retrovirus-like elements, RTVL-H, are heterogeneous in their ability to regulate the expression of linked genes. Although all of five LTRs tested could promote expression of the chloramphenicol acetyltransferase (CAT) gene, their relative promoter activities as well as range of activities varied widely. Several of the LTRs tested also exhibited bidirectional promoter activity either alone or when activated by an SV40 early enhancer. One LTR, H6, displayed strong promoter activity in human (NTera2D1, 293, Hep2), monkey (COS-1), and mouse (3T3) cells. In fact, the activity of this LTR was similar to that of the SV40 early promoter/enhancer in 293, COS-1, and 3T3 cells. RNA mapping studies have localized the transcription start site to the expected location in the H6 LTR. RTVL-H LTRs were also shown to contain sequences which could increase transcription from the human beta-globin promoter and be influenced by SV40 enhancer sequences. As the human genome contains several hundred related RTVL-H sequences and a similar number of solitary LTRs, these findings raise the possibility that RTVL-H LTRs could have diverse effects on the expression of adjacent cellular genes.
人类基因组包含多种在结构上与逆转录病毒和逆转座子相似的元件。我们已经表明，一大类人类逆转录病毒样元件RTVL-H的长末端重复序列（LTR）在调节连锁基因表达的能力上是异质的。尽管所测试的五个LTR都能促进氯霉素乙酰转移酶（CAT）基因的表达，但其相对启动子活性以及活性范围差异很大。所测试的几个LTR单独或在被SV40早期增强子激活时也表现出双向启动子活性。一个LTR，即H6，在人（NTera2D1、293、Hep2）、猴（COS-1）和小鼠（3T3）细胞中表现出很强的启动子活性。事实上，在293、COS-1和3T3细胞中，这个LTR的活性与SV40早期启动子/增强子的活性相似。RNA定位研究已将转录起始位点定位到H6 LTR中的预期位置。RTVL-H LTRs还显示含有可增加人β-珠蛋白启动子转录并受SV40增强子序列影响的序列。由于人类基因组包含数百个相关的RTVL-H序列以及数量相近的单个LTR，这些发现增加了RTVL-H LTRs可能对相邻细胞基因的表达产生多种影响的可能性。
