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Publication : High-resolution genome-wide mapping of transposon integration in mammals.

First Author  Yant SR Year  2005
Journal  Mol Cell Biol Volume  25
Issue  6 Pages  2085-94
PubMed ID  15743807 Mgi Jnum  J:97511
Mgi Id  MGI:3575587 Doi  10.1128/MCB.25.6.2085-2094.2005
Citation  Yant SR, et al. (2005) High-resolution genome-wide mapping of transposon integration in mammals. Mol Cell Biol 25(6):2085-94
abstractText  The Sleeping Beauty (SB) transposon is an emerging tool for transgenesis, gene discovery, and therapeutic gene delivery in mammals. Here we studied 1,336 SB insertions in primary and cultured mammalian cells in order to better understand its target site preferences. We report that, although widely distributed, SB integration recurrently targets certain genomic regions and shows a small but significant bias toward genes and their upstream regulatory sequences. Compared to those of most integrating viruses, however, the regional preferences associated with SB-mediated integration were much less pronounced and were not significantly influenced by transcriptional activity. Insertions were also distinctly nonrandom with respect to intergenic sequences, including a strong bias toward microsatellite repeats, which are predominantly enriched in noncoding DNA. Although we detected a consensus sequence consistent with a twofold dyad symmetry at the target site, the most widely used sites did not match this consensus. In conjunction with an observed SB integration preference for bent DNA, these results suggest that physical properties may be the major determining factor in SB target site selection. These findings provide basic insights into the transposition process and reveal important distinctions between transposon- and virus-based integrating vectors.
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