Abstract:
:The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neuronal lineage and cause somatic mosaicism. Although DNA methylation mediates L1 promoter repression, the temporal pattern of methylation applied to individual RC-L1s during neurogenesis is unclear. Here, we identified a de novo L1 insertion in a human induced pluripotent stem cell (hiPSC) line via retrotransposon capture sequencing (RC-seq). The L1 insertion was full-length and carried 5' and 3' transductions. The corresponding donor RC-L1 was part of a large and recently active L1 transduction family and was highly mobile in a cultured-cell L1 retrotransposition reporter assay. Notably, we observed distinct and dynamic DNA methylation profiles for the de novo L1 and members of its extended transduction family during neuronal differentiation. These experiments reveal how a de novo L1 insertion in a pluripotent stem cell is rapidly recognized and repressed, albeit incompletely, by the host genome during neurodifferentiation, while retaining potential for further retrotransposition.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Salvador-Palomeque C,Sanchez-Luque FJ,Fortuna PRJ,Ewing AD,Wolvetang EJ,Richardson SR,Faulkner GJdoi
10.1128/MCB.00499-18subject
Has Abstractpub_date
2019-03-19 00:00:00issue
7eissn
0270-7306issn
1098-5549pii
MCB.00499-18journal_volume
39pub_type
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