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Integrase-Specific Enhancement and Suppression of Retroviral DNA Integration by Compacted Chromatin Structure In Vitro

Taganov, Konstantin D. and Cuesta, Isabel and Daniel, René and Cirillo, Lisa Ann and Katz, Richard A. and Zaret, Kenneth S. and Skalka, Anne Marie (2004) Integrase-Specific Enhancement and Suppression of Retroviral DNA Integration by Compacted Chromatin Structure In Vitro. Journal of Virology, 78 (11). pp. 5848-5855. ISSN 0022-538X. doi:10.1128/JVI.78.11.5848-5855.2004.

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Integration of viral DNA into the host chromosome is an obligatory step in retroviral replication and is dependent on the activity of the viral enzyme integrase. To examine the influence of chromatin structure on retroviral DNA integration in vitro, we used a model target comprising a 13-nucleosome extended array that includes binding sites for specific transcription factors and can be compacted into a higher-ordered structure. We found that the efficiency of in vitro integration catalyzed by human immunodeficiency virus type 1 (HIV-1) integrase was decreased after compaction of this target with histone H1. In contrast, integration by avian sarcoma virus (ASV) integrase was more efficient after compaction by either histone H1 or a high salt concentration, suggesting that the compacted structure enhances this reaction. Furthermore, although site-specific binding of transcription factors HNF3 and GATA4 blocked ASV DNA integration in extended nucleosome arrays, local opening of H1-compacted chromatin by HNF3 had no detectable effect on integration, underscoring the preference of ASV for compacted chromatin. Our results indicate that chromatin structure affects integration site selection of the HIV-1 and ASV integrases in opposite ways. These distinct properties of integrases may also affect target site selection in vivo, resulting in an important bias against or in favor of integration into actively transcribed host DNA.

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Additional Information:Copyright © 2004, American Society for Microbiology. Received 18 September 2003/ Accepted 23 January 2004 We thank G. Merkel and D. Colleluori for providing purified ASV and HIV-1 integrases. This work was supported by National Institutes of Health grants AI40385, CA71515, CA06927, and GM47903; by the Mathers Charitable Foundation; and also by an appropriation from the Commonwealth of Pennsylvania. The following Fox Chase Cancer Center Shared Facilities were used in the course of this work: Cell Culture Facility, Biochemistry and Biotechnology Facility (DNA Synthesis), and Research Secretarial Services. The contents of this report 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.
Issue or Number:11
Record Number:CaltechAUTHORS:TAGjvir04
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:3275
Deposited By: Archive Administrator
Deposited On:25 May 2006
Last Modified:08 Nov 2021 19:54

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