DNA bending creates favored sites for retroviral integration: an explanation for preferred insertion sites in nucleosomes
Open accessAbstract
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.
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PIC or intasome have greater inclination to integrate into bent target DNA wrapped with histones or transcription factors compared to naked DNA.
“It has been observed that PIC or the intasome have greater inclination to integrate into bent target DNA that is wrapped with histones or transcription factors in comparison to the naked DNA (Müller and Varmus 1994, Pruss et al. 1994, Maskell et al. 2015, Matysiak et al. 2017).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Müller and Varmus 1994
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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
- Published
- 1994-10-01
- Volume
- 13
- Issue
- 19
- Pages
- 4704-4714
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- 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
- 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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