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Science 13 June 2003:
Vol. 300. no. 5626, pp. 1749 - 1751
DOI: 10.1126/science.1083413
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Reports

Transcription Start Regions in the Human Genome Are Favored Targets for MLV Integration

Xiaolin Wu,1 Yuan Li,2 Bruce Crise,2 Shawn M. Burgess1*

Factors contributing to retroviral integration have been intractable because past studies have not precisely located genomic sites of proviruses in sufficient numbers for significant analysis. In this study, 903 murine leukemia virus (MLV) and 379 human immunodeficiency virus–1 (HIV-1) integrations in the human genome were mapped. The data showed that MLV preferred integration near the start of transcriptional units (either upstream or downstream) whereas HIV-1 preferred integration anywhere in the transcriptional unit but not upstream of the transcriptional start. Defining different integration site preferences for retroviruses will have important ramifications for gene therapy and may aid in our understanding of the factors directing the integration process.

1 Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892–8004, USA.
2 Science Applications International Corporation–Frederick, Frederick, MD 21702, USA.

* To whom correspondence should be addressed. E-mail: burgess{at}mail.nih.gov

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Stable gene transfer and expression in human primary T cells by the Sleeping Beauty transposon system.
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Blood 107, 483-491
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Structure-based prediction of insertion-site preferences of transposons into chromosomes..
A. M. Geurts, C. S. Hackett, J. B. Bell, T. L. Bergemann, L. S. Collier, C. M. Carlson, D. A. Largaespada, and P. B. Hackett (2006)
Nucleic Acids Res. 34, 2803-2811
   Abstract »    Full Text »    PDF »
Identification of Potential Human Oncogenes by Mapping the Common Viral Integration Sites in Avian Nephroblastoma.
P. Pajer, V. Pecenka, J. Kralova, V. Karafiat, D. Prukova, Z. Zemanova, R. Kodet, and M. Dvorak (2006)
Cancer Res. 66, 78-86
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Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity.
C. Lagresle-Peyrou, F. Yates, M. Malassis-Seris, C. Hue, E. Morillon, A. Garrigue, A. Liu, P. Hajdari, D. Stockholm, O. Danos, et al. (2006)
Blood 107, 63-72
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Seeing is believing: Structure of the catalytic domain of HIV-1 integrase in complex with human LEDGF/p75.
C. M. Bradley and R. Craigie (2005)
PNAS 102, 17543-17544
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Somatic integration of an oncogene-harboring Sleeping Beauty transposon models liver tumor development in the mouse.
C. M. Carlson, J. L. Frandsen, N. Kirchhof, R. S. McIvor, and D. A. Largaespada (2005)
PNAS 102, 17059-17064
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Hopping around the Tumor Genome: Transposons for Cancer Gene Discovery.
L. S. Collier and D. A. Largaespada (2005)
Cancer Res. 65, 9607-9610
   Abstract »    Full Text »    PDF »
Simian Immunodeficiency Virus Integration Preference Is Similar to That of Human Immunodeficiency Virus Type 1.
B. Crise, Y. Li, C. Yuan, D. R. Morcock, D. Whitby, D. J. Munroe, L. O. Arthur, and X. Wu (2005)
J. Virol. 79, 12199-12204
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