L1 retrotransposition in nondividing and primary human somatic cells.
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 G1/S-arrested cells, resulting in retrotransposition in both cases; however, it was not detected in G0-arrested cells. Thus, these data indicate that L1 retrotransposition can occur in nondividing somatic cells.
Kubo
Shuji
S
Department of Medicine, UCLA School of Medicine, 675 Charles E. Young Drive South, MRL-1551, Los Angeles, CA 90095-7019, USA.
Seleme
Maria Del Carmen
MC
Soifer
Harris S
HS
Perez
José Luis Garcia
JL
Moran
John V
JV
Kazazian
Haig H
HH
Kasahara
Noriyuki
N
D000256:Adenoviridae / Q000235:genetics; D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010735:Phosphoglycerate Kinase / Q000378:metabolism; D018626:Retroelements; D014162:Transfection
D004791:Enzyme Inhibitors; D018626:Retroelements; D010735:Phosphoglycerate Kinase