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Integrase-specific enhancement and suppression of retroviral DNA integration by compacted chromatin structure in vitro. J Virol 2004 Jun;78(11):5848-55

Date

05/14/2004

Pubmed ID

15140982

Pubmed Central ID

PMC415796

DOI

10.1128/JVI.78.11.5848-5855.2004

Scopus ID

2-s2.0-2442707756   46 Citations

Abstract

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.

Author List

Taganov KD, Cuesta I, Daniel R, Cirillo LA, Katz RA, Zaret KS, Skalka AM

Author

Lisa A. Cirillo PhD Assistant Dean, Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Avian Sarcoma Viruses
Binding Sites
Chromatin
DNA-Binding Proteins
GATA4 Transcription Factor
HIV Integrase
Hepatocyte Nuclear Factor 3-alpha
Integrases
Nuclear Proteins
Nucleosomes
Retroviridae
Transcription Factors
Virus Integration