Cited by 42Genomics and Chromatin DynamicsHIV Research and TreatmentDNA and Nucleic Acid Chemistry

Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer

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Wilson, Marcus D., Renault, Ludovic, Maskell, Daniel P., Ghoneim, Mohamed, Pye, Valerie E., Nans, Andrea, Rueda, David S., Cherepanov, Peter +1 more·2019·Nature Communications

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Abstract

Retroviral integrase can efficiently utilise nucleosomes for insertion of the reverse-transcribed viral DNA. In face of the structural constraints imposed by the nucleosomal structure, integrase gains access to the scissile phosphodiester bonds by lifting DNA off the histone octamer at the site of integration. To clarify the mechanism of DNA looping by integrase, we determined a 3.9 Å resolution structure of the prototype foamy virus intasome engaged with a nucleosome core particle. The structural data along with complementary single-molecule Förster resonance energy transfer measurements reveal twisting and sliding of the nucleosomal DNA arm proximal to the integration site. Sliding the nucleosomal DNA by approximately two base pairs along the histone octamer accommodates the necessary DNA lifting from the histone H2A-H2B subunits to allow engagement with the intasome. Thus, retroviral integration into nucleosomes involves the looping-and-sliding mechanism for nucleosomal DNA repositioning, bearing unexpected similarities to chromatin remodelers.

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  • Cryo-EM structures of the PFV intasome bound to a mononucleosome show that the nucleosome adapts to present DNA in a conformation optimal for strand transfer.

    “Cryo-EM structures of the PFV intasome engaged with a mononucleosome revealed that the latter adapts to present the DNA in a conformation optimal for strand transfer64,65.”

    From Structure and function of retroviral integrase (2022) · cites this paper as [65]

  • The intasome forms a multivalent interface with the nucleosome, contacting both nucleosomal DNA gyres and the core histones.

    “The intasome forms a multivalent interface with the nucleosome, contacting both nucleosomal DNA gyres and the core histones (Fig. 4).”

    From Structure and function of retroviral integrase (2022) · cites this paper as [65]

  • These interactions are thought to offset the energy needed to shift nucleosomal DNA along the histone octamer core to create slack for lifting target DNA at the integration site.

    “These interactions are thought to offset the energy required to shift nucleosomal DNA along the histone octamer core to create the slack for lifting the target DNA at the site of integration (Fig. 4)65.”

    From Structure and function of retroviral integrase (2022) · cites this paper as [65]

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Authors
Wilson, M. D., Renault, L., Maskell, D. P., Ghoneim, M., Pye, V. E., Nans, A., Rueda, D. S., Cherepanov, P., & Costa, A.
Affiliations
  • The Francis Crick Institute (GB)
  • Leiden University (NL)
  • University of Leeds (GB)
  • MRC London Institute of Medical Sciences (GB)
Corresponding author
  • Rueda, David S.
  • Cherepanov, Peter
  • Costa, Alessandro
Venue
Nature Communications
Published
2019-09-13
Volume
10
Issue
1
Pages
4189-4189
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2973154821
Cited by
42
References
80
Citations by year
2026: 5 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 14 · 2020: 7 · 2019: 1
FWCI
2.23
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
  • The Francis Crick Institute (cc-by)
Funders
  • Wellcome Trust (Z/17/Z, 820102, FC0010065, 206292/Z/17/Z, 206292)
  • Francis Crick Institute (10015, 10065, 10654, 10061)
  • UK Research and Innovation (MC-A658-5TY10)
  • Cancer Research UK (820102, FC0010065)
  • Leverhulme Trust (RPG-2016-214, RPG-2016)
  • European Commission (HORIZON2020)
  • Medical Research Council (820102, MC-A658-5TY10, FC0010065, UKRI MC-A658-5TY10)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
retroviral integrase, nucleosome, DNA looping, DNA sliding, histone octamer, intasome, foamy virus, chromatin remodeling, reverse transcription, histone H2A-H2B
MeSH terms
DNA, Histones, Humans, Nucleoproteins, Nucleosomes, Cryoelectron Microscopy, Protein Structure, Quaternary, Fluorescence Resonance Energy Transfer

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