Narezkina, Anna and Taganov, Konstantin D. and Litwin, Samuel and Stoyanova, Radka and Hayashi, Junpei and Seeger, Christoph and Skalka, Anna Marie and Katz, Richard A. (2004) Genome-Wide Analyses of Avian Sarcoma Virus Integration Sites. Journal of Virology, 78 (21). pp. 11656-11663. ISSN 0022-538X http://resolver.caltech.edu/CaltechAUTHORS:NARjvir04
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The chromosomal features that influence retroviral integration site selection are not well understood. Here, we report the mapping of 226 avian sarcoma virus (ASV) integration sites in the human genome. The results show that the sites are distributed over all chromosomes, and no global bias for integration site selection was detected. However, RNA polymerase II transcription units (protein-encoding genes) appear to be favored targets of ASV integration. The integration frequency within genes is similar to that previously described for murine leukemia virus but distinct from the higher frequency observed with human immunodeficiency virus type 1. We found no evidence for preferred ASV integration sites over the length of genes and immediate flanking regions. Microarray analysis of uninfected HeLa cells revealed that the expression levels of ASV target genes were similar to the median level for all genes represented in the array. Although expressed genes were targets for integration, we found no preference for integration into highly expressed genes. Our results provide a more detailed description of the chromosomal features that may influence ASV integration and support the idea that distinct, virus-specific mechanisms mediate integration site selection. Such differences may be relevant to viral pathogenesis and provide utility in retroviral vector design.
|Additional Information:||Copyright © 2004, American Society for Microbiology. Received 31 March 2004/ Accepted 28 June 2004. We are grateful to Peter Adams, Glenn Rall, and Ken Zaret for critical comments on the manuscript. We acknowledge the following Fox Chase Cancer Center Core Facilities and individuals for excellent technical assistance: Automated DNA Sequencing Facility (Anita Cywinski), Biostatistics Facility, DNA Microarray Facility (Ketaki Datta), and The Fannie E. Rippel Biochemistry and Biotechnology Facility. We also thank Marie Estes for excellent assistance in preparing the manuscript. This work was supported by National Institutes of Health grants AI40385, CA71515, CA06927, AI30544, and AI48046 and also by an appropriation from the Commonwealth of Pennsylvania. Partial support for R.A.K. was provided by a grant from the American Cancer Society (IRG-92-027-05). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute or any other sponsoring organization.|
|Subject Keywords:||RETROVIRAL DNA INTEGRATION; HUMAN TRANSCRIPTOME MAP; I-HYPERSENSITIVE SITES; CHROMATIN-STRUCTURE; CDNA INTEGRATION; EXPRESSED GENES; TYPE-1; TARGETS; CELLS; SELECTION|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Lindsay Cleary|
|Deposited On:||21 Jun 2006|
|Last Modified:||26 Dec 2012 08:55|
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