Cited by 202Genomics and Chromatin DynamicsDNA and Nucleic Acid ChemistryHIV Research and Treatment

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DNA bending creates favored sites for retroviral integration: an explanation for preferred insertion sites in nucleosomes

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Müller, H.P., Varmus, H.E.·1994·The EMBO Journal

DOI 10.1002/j.1460-2075.1994.tb06794.xPMC PMC395405

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Abstract

The choice of retroviral integration sites is strongly influenced by chromatin: integration in vitro occurs more efficiently into nucleosomal DNA than into naked DNA, and a characteristic pattern of preferred insertion sites with a 10 bp periodicity is observed at the outer face of the nucleosomal DNA. At least three features of nucleosomal DNA could be responsible for the creation of these favored sites: the presence of histones, attachment of the DNA to a protein surface, and DNA bending. To test each of these possibilities, we studied integration in vitro with human immunodeficiency virus and murine leukemia virus integrases into four model targets that mimic features of nucleosomal DNA: (i) catabolite activator protein-DNA complexes; (ii) lac repressor-operator complexes; (iii) lac repressor-induced loops; and (iv) intrinsically bent A-tract DNA. We found that bending of the target DNA can create favored integration sites at the outer face of the helix, irrespective of whether the bent DNA is attached to a protein surface. Our findings offer an explanation for the preferred usage of nucleosomes as integration targets. In addition, they suggest that bending of the target DNA might be an intrinsic feature of the integration reaction.

Integrity signals

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Crossref · 10.1002/j.1460-2075.1994.tb06794.x

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Authors: Müller, H. P., & Varmus, H. E.
Affiliations: University of California, San Francisco (US)
ORCID: Varmus, H.E.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1994-10-01
Volume: 13
Issue: 19
Pages: 4704-4714
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1994.tb06794.x
PMC: PMC395405
OpenAlex: W1464706687
Cited by: 202
References: 49
Citations by year: 2026: 1 · 2025: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 4
FWCI: 3.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords: retroviral integration, DNA bending, nucleosome, HIV integrase, chromatin, histones, catabolite activator protein, DNA loops
MeSH terms: Base Sequence, Cyclic AMP Receptor Protein, DNA, DNA Nucleotidyltransferases, DNA-Binding Proteins, HIV, Models, Molecular, Molecular Sequence Data, Leukemia Virus, Murine, Nucleic Acid Conformation, Nucleosomes, Repressor Proteins, Retroviridae, Virus Integration, Integrases

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DNA bending creates favored sites for retroviral integration: an explanation for preferred insertion sites in nucleosomes

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