title: Genome-Wide Analysis of Transposon and Retroviral Insertions Reveals Preferential Integrations in Regions of DNA Flexibility.
abstract: DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germ-line transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish with Tol2 transposon and retroviral integration sites. Genome-wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our findings show that structural features influence the integration of heterologous DNA in genomes, and have implications for targeted genome engineering.
authors.affiliation: Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AJ, United Kingdom.
authors.forename: Pavle
authors.initials: P
authors.lastname: Vrljicak
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Shijie
authors.initials: S
authors.lastname: Tao
authors.affiliation: National Human Genome Research Institute, Bethesda, Maryland 20892-8004.
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Varshney
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Helen Ngoc Bao
authors.initials: HN
authors.lastname: Quach
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, 117604, Singapore.
authors.forename: Adita
authors.initials: A
authors.lastname: Joshi
authors.affiliation: National Human Genome Research Institute, Bethesda, Maryland 20892-8004.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: LaFave
authors.affiliation: National Human Genome Research Institute, Bethesda, Maryland 20892-8004 K.Sampath@warwick.ac.uk.
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Burgess
authors.affiliation: Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AJ, United Kingdom K.Sampath@warwick.ac.uk.
authors.forename: Karuna
authors.identifier: 0000-0002-0729-1977
authors.initials: K
authors.lastname: Sampath
mesh_terms: D000818:Animals; D001483:Base Sequence; D004251:DNA Transposable Elements; D018390:Gene Targeting; D005818:Genetic Engineering; D016678:Genome; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D016254:Mutagenesis, Insertional; D059372:Nucleotide Motifs; D012091:Repetitive Sequences, Nucleic Acid; D012190:Retroviridae / Q000235:genetics*; D016662:Virus Integration; D015027:Zebrafish / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements
keywords: Ac/Ds; ES cells; MMLV; Tol2; functional genomics; gene targeting; genome engineering; genome-wide analysis; integrations; mouse; retrovirus; transposon; vertebrate genomes; zebrafish
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