Structure-based prediction of insertion-site preferences of transposons into chromosomes

Aron M. Geurts, Christopher S. Hackett, Jason B. Bell, Tracy L. Bergemann, Lara S. Collier, Corey M. Carlson, David A Largaespada, Perry B Hackett

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Mobile genetic elements with the ability to integrate genetic information into chromosomes can cause disease over short periods of time and shape genomes over eons. These elements can be used for functional genomics, gene transfer and human gene therapy. However, their integration-site preferences, which are critically important for these uses, are poorly understood. We analyzed the insertion sites of several transposons and retroviruses to detect patterns of integration that might be useful for prediction of preferred integration sites. Initially we found that a mathematical description of DNA-deformability, called Vstep, could be used to distinguish preferential integration sites for Sleeping Beauty (SB) transposons into a particular 100 bp region of a plasmid [G. Liu, A. M. Geurts, K. Yae, A. R. Srinivassan, S. C. Fahrenkrug, D. A. Largaespada,J. Takeda, K. Horie, W. K. Olson and P. B. Hackett (2005) J. Mol. Biol., 346, 161-173]. Based on these findings, we extended our examination of integration of SB transposons into whole plasmids and chromosomal DNA. To accommodate sequences up to 3 Mb for these analyses, we developed an automated method, ProTIS

Original languageEnglish (US)
Pages (from-to)2803-2811
Number of pages9
JournalNucleic acids research
Volume34
Issue number9
DOIs
StatePublished - 2006

Bibliographical note

Funding Information:
The authors thank the Arnold and Mabel Beckman Foundation for supporting their work and all members of the Beckman Center for Transposon Research for a long history of contributions of ideas and results. The authors are especially grateful to Drs Michael Simmons, Reuben Harris, William A. Weiss (UCSF) and Elena Aronovich for careful reading of the manuscript, Dr Keiko Akagi (NCI) for mapping the T2/Onc integrations, Michael H. L Lee for technical assistance and Joe Carlson (Berkeley Drosophila Genome Project) for sending P-element datasets. The authors were also supported by NIH grants 1PO1 HD32652-07 and R43 HL076908-01 (P.B.H.) and DA014764 (D.A.L.) and T32 HD007480 (A.M.G.), NIGMS GM008568 (C.S.H.) and NCI T32CA09138-28 (L.S.C. and C.M.C.) and F32CA10619-01 (L.S.C.). Funding to pay the Open Access publication charges for this article was provided by NIH.

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