Alves G, Tatro A, Fanning T
Department of Cellular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Gene. 1996 Oct 17;176(1-2):39-44. doi: 10.1016/0378-1119(96)00205-3.
Long interspersed element-1 (LINE-1) retrotransposons from Homo sapiens (L1Hs) are not expressed in normal somatic cells. In malignant cells, there is a direct correlation between the hypomethylation of 5' L1Hs sequences and the presence of L1Hs proteins, suggesting that elements with hypomethylated 5' ends are transcriptionally active. Sequences flanking the 5' ends of hypomethylated L1Hs elements were isolated from the T-47D breast cancer cell line by inverse-PCR and cloning. These flanker clones served as probes for analyzing the loci harboring the hypomethylated L1Hs elements. Sequencing demonstrated that the flankers have no homology with one another and do not appear to contain common short motifs that might serve as recognition sites for regulatory factors. The hypomethylated L1Hs elements are located on many chromosomes, although three of twelve are on chromosome 15. Southern blotting indicates that certain elements are hypomethylated in numerous cell lines, and that elements that are hypomethylated in malignant germ cells comprise a different subset of elements than those that are hypomethylated in non-germ cell malignancies. These results suggest that the subset of L1Hs elements that is hypomethylated in malignant cells is not simply a random collection of L1Hs elements.
来自智人的长散在元件1（LINE-1，L1Hs）逆转录转座子在正常体细胞中不表达。在恶性细胞中，5' L1Hs序列的低甲基化与L1Hs蛋白的存在之间存在直接相关性，这表明5' 末端低甲基化的元件具有转录活性。通过反向PCR和克隆从T-47D乳腺癌细胞系中分离出低甲基化L1Hs元件5' 末端侧翼的序列。这些侧翼克隆用作分析含有低甲基化L1Hs元件的基因座的探针。测序表明，这些侧翼序列彼此之间没有同源性，并且似乎不包含可能作为调控因子识别位点的常见短基序。低甲基化的L1Hs元件位于许多染色体上，尽管12条染色体中的3条位于15号染色体上。Southern印迹分析表明，某些元件在许多细胞系中是低甲基化的，并且在恶性生殖细胞中低甲基化的元件与在非生殖细胞恶性肿瘤中低甲基化的元件组成不同的元件子集。这些结果表明，在恶性细胞中低甲基化的L1Hs元件子集并非简单地是L1Hs元件的随机集合。
