Nucleosomes, DNA-binding proteins, and DNA sequence modulate retroviral integration target site selection

Integration of retroviral DNA can serve as a paradigm for cellular functions that are affected by the packaging of DNA into chromatin. We have used a novel polymerase chain reaction-based assay to survey DNA and chromatin for the precise distribution of many integration sites. Integration into naked...

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Veröffentlicht in:Cell 1992-05, Vol.69 (5), p.769-780
Hauptverfasser: Pryciak, Peter M., Varmus, Harold E.
Format: Artikel
Sprache:eng
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Zusammenfassung:Integration of retroviral DNA can serve as a paradigm for cellular functions that are affected by the packaging of DNA into chromatin. We have used a novel polymerase chain reaction-based assay to survey DNA and chromatin for the precise distribution of many integration sites. Integration into naked DNA targets is nonuniform, implying a nucleotide sequence bias. In chromatin, integration occurs preferentially at postitions where the major groove is on the exposed face of the nucleosomal DNA helix, generating a 10 bp periodic spacing of preferred sites. Chromatin assembly enhances the reactivity of many sites, so that integration occurs most frequently at sites in nucleosomal, rather than nucleosome-free, regions of minichromosomes. In contrast, integration is prevented in a region occupied by a site-specific DNA-binding protein. Comparisons of integration events mediated by viral nucleoprotein complexes or by two different retroviral integrases show that the integration machinery also affects target site selection.
ISSN:0092-8674
1097-4172
DOI:10.1016/0092-8674(92)90289-O