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Molecular and Cellular Biology, March 2005, p. 2085-2094, Vol. 25, No. 6
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.6.2085-2094.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

High-Resolution Genome-Wide Mapping of Transposon Integration in Mammals

Stephen R. Yant,1 Xiaolin Wu,2 Yong Huang,1 Brian Garrison,1 Shawn M. Burgess,3 and Mark A. Kay1*

Departments of Pediatrics and Genetics, Stanford University School of Medicine, Stanford, California,1 Laboratory of Molecular Technology, SAIC—Frederick, National Cancer Institute—Frederick, Frederick,2 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland3

Received 8 October 2004/ Returned for modification 15 November 2004/ Accepted 15 December 2004

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.

* Corresponding author. Mailing address: Stanford University School of Medicine, Department of Pediatrics, 300 Pasteur Dr., Room G-305, Stanford, CA 94305-5208. Phone: (650) 498-6531. Fax: (650) 498-6540. E-mail: markay{at}stanford.edu.

Molecular and Cellular Biology, March 2005, p. 2085-2094, Vol. 25, No. 6
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.6.2085-2094.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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