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MLV integration site selection is driven by strong enhancers and active promoters
Open accessAbstract
Retroviruses integrate into the host genome in patterns specific to each virus. Understanding the causes of these patterns can provide insight into viral integration mechanisms, pathology and genome evolution, and is critical to the development of safe gene therapy vectors. We generated murine leukemia virus integrations in human HepG2 and K562 cells and subjected them to second-generation sequencing, using a DNA barcoding technique that allowed us to quantify independent integration events. We characterized >3 700 000 unique integration events in two ENCODE-characterized cell lines. We find that integrations were most highly enriched in a subset of strong enhancers and active promoters. In both cell types, approximately half the integrations were found in <2% of the genome, demonstrating genomic influences even narrower than previously believed. The integration pattern of murine leukemia virus appears to be largely driven by regions that have high enrichment for multiple marks of active chromatin; the combination of histone marks present was sufficient to explain why some strong enhancers were more prone to integration than others. The approach we used is applicable to analyzing the integration pattern of any exogenous element and could be a valuable preclinical screen to evaluate the safety of gene therapy vectors.
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“The well-understood integration preferences of HIV-1 for active transcription units72 and MLV for promoter/enhancer regions73–75 are in large part dictated via specific interactions of the respective IN proteins with chromatin-bound host factors.”
From Structure and function of retroviral integrase (2022) · cites this paper as [75]
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“BET proteins significantly stimulate γ-retroviral IN strand transfer activities in vitro67,115,116 and appear to act as bimodal tethers to direct PICs to preferred genomic locations74,75,114,117,118.”
From Structure and function of retroviral integrase (2022) · cites this paper as [75]
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
ggplot2: Elegant Graphics for Data Analysis
Wickham, H. (2009) · doi:10.1007/978-0-387-98141-3 · Cited by 14,447
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129
Mapping and analysis of chromatin state dynamics in nine human cell types
Ernst, J., Kheradpour, P., Mikkelsen, T. S., Shoresh, N., Ward, L. D., Epstein, C. B., Zhang, X., Wang, L., Issner, R., Coyne, M., et al. (2011) · Nature · doi:10.1038/nature09906 · Cited by 2,898
Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
Hacein-Bey-Abina, S., Garrigue, A., Wang, G. P., Soulier, J., Lim, A., Morillon, E., Clappier, E., Caccavelli, L., Delabesse, E., Beldjord, K., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci35700 · Cited by 1,854
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Items 101–116 of 116
Peer Review #2 of "Enhort: a platform for deep analysis of genomic positions (v0.1)"
(2019) · PeerJ Computer Science · doi:10.7287/peerj-cs.198v0.1/reviews/2
Hogan, D. J., Zhu, J., Diago, O. R., Gammon, D., Haghighi, A. N., Lu, G., Das, A., Gruber, H. E., Jolly, D. J., & Ostertag, D. G. (2023) · doi:10.1158/1078-0432.22470572.v1
Alquezar‐Planas, D. E. (2023) · Technical Reports of the Australian Museum online · doi:10.3853/j.1835-4211.38.2023.1835
rAAV Integration: Detection and Risk Assessment
Yuan, J., Gil-Fariña, I., Fronza, R., & Whiteley, L. O. (2024) · Wiley eBooks · doi:10.1002/9781119852810.ch13
Akkawi, C., Feuillard, J., Leon-Diaz, F., Belkhir, K., Godefroy, N., Péloponèse, J., Mougel, M., & Lainé, S. (2023) · Figshare · doi:10.6084/m9.figshare.24130110
Akkawi, C., Feuillard, J., Leon-Diaz, F., Belkhir, K., Godefroy, N., Péloponèse, J., Mougel, M., & Lainé, S. (2023) · Figshare · doi:10.6084/m9.figshare.24130107
Miklík, D., Slavková, M., Kučerová, D., Mekadim, C., Mrázek, J., & Hejnar, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.30.596639
Wells, D., Guo, S., Shao, W., Bale, M. J., Coffin, J. M., Hughes, S. H., & Wu, X. (2020) · Figshare · doi:10.6084/m9.figshare.11960178
Identification de facteurs cellulaires régulant la rétrotransposition de Ty1 chez S. cerevisiae
Barkova, A. (2019) · theses.fr (ABES) · doi:10.70675/d3dce78az48e8z4209zb2afzd31c32c110b1
Nuclear envelope and nuclear response to mechanical deformation
Williart, A. (2023) · theses.fr (ABES) · doi:10.70675/e08139d8z12d5z47c0z9929z79b060a48d58
Singh, P. (2026) · Harvard Dataverse · doi:10.7910/dvn/udt6uc
Processed HIV-1 integration site datasets from Jurkat cells with capsid mutants
Singh, P. (2026) · Harvard Dataverse · doi:10.7910/dvn/xrkmnr
Metadata
- Authors
- LaFave, M. C., Varshney, G. K., Gildea, D. E., Wolfsberg, T. G., Baxevanis, A. D., & Burgess, S. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Burgess, Shawn M.
- ORCID
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01-23
- Volume
- 42
- Issue
- 7
- Pages
- 4257-4269
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3985626
- OpenAlex
- W2034118113
- Cited by
- 114
- References
- 47
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 20 · 2015: 15 · 2014: 8
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- Locations
- Nucleic Acids Research (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- murine leukemia virus, retroviral integration, integration site selection, enhancers, histone modifications, active chromatin, DNA barcoding, HepG2 cells, K562 cells, integration hotspots
- MeSH terms
- Attachment Sites, Microbiological, Enhancer Elements, Genetic, Humans, Moloney murine leukemia virus, Promoter Regions, Genetic, Virus Integration, K562 Cells, Cell Line, Tumor
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