L1 retrotransposition in nondividing and primary human somatic cells
L1 retrotransposition in nondividing and primary human somatic cells
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DOI：
10.1073/pnas.0601954103
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发表时间：
2006-05-23
影响因子：
11.1
通讯作者：
Kasahara, Noriyuki
中科院分区：
文献类型：
--
作者：
Kubo, Shuji;del Carmen Seleme, Maria;Kasahara, Noriyuki
在静止、未分裂和/或终末分化的体细胞中，是否会发生长时间穿插的Element-1(L1或Line-1)逆转录转座，一直是人类遗传学中一个尚未回答的基本问题。在这里，我们使用了一个普遍存在的活性磷酸甘油酸激酶-1启动子来驱动来自腺病毒-L1杂交载体的高活性人类L1元件的表达。该载体系统在高达91%的活跃生长的永生化细胞中实现了逆转录转座，我们证明L1逆转录转座可以被逆转录酶抑制剂3‘-叠氮-3’-脱氧胸苷抑制。这种腺病毒载体能够有效地将L1元件转移到分化的原代人类体细胞和G(1)/S滞留细胞中，导致这两种情况下的逆转录转座；然而，在G(0)滞留细胞中没有检测到L1元件。因此，这些数据表明L1逆转录转座可以发生在未分裂的体细胞中。
Whether long interspersed element-1 (L1 or LINE-1) retrotransposition can occur in quiescent, nondividing, and/or terminally differentiated somatic cells has remained an unanswered fundamental question in human genetics. Here, we used a ubiquitously active phosphoglycerate kinase-1 promoter to drive the expression of a highly active human L1 element from an adenovirus-L1 hybrid vector. This vector system achieved retrotransposition in up to 91% of actively growing immortalized cells, and we demonstrated that L1 retrotransposition can be suppressed by the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine. This adenovirus vector enabled efficient delivery of the L1 element into differentiated primary human somatic cells and G(1)/S-arrested cells, resulting in retrotransposition in both cases; however, it was not detected in G(0)-arrested cells. Thus, these data indicate that L1 retrotransposition can occur in nondividing somatic cells.