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The site of HIV-1 integration in the human genome determines basal transcriptional activity and response to Tat transactivation
Open accessAbstract
Because of the heterogeneity of chromatin, the site of integration of human immunodeficiency virus (HIV) in the genome could have dramatic effects on its transcriptional activity. We have used an HIV-1-derived retroviral vector, in which the green fluorescent protein is under the control of the HIV promoter, to generate by infection 34 Jurkat clonal cell lines each containing a single integration of the HIV-1 vector. In the absence of Tat, a 75-fold difference in expression level between the highest and lowest expressing clones was observed. Basal promoter activity was low in 80% of the clones and moderate to high in the remaining 20% of clones. We found that differences in expression levels are due to the integration site and are not controlled by DNA methylation or histone acetylation. Tat activated transcription in each clone, and an inverse correlation was observed between basal transcriptional activity and inducibility by Tat. These observations demonstrate that the chromatin environment influences basal HIV gene expression and that the HIV Tat protein activates transcription independently of the chromatin environment.
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“However, it is now becoming clearer that certain retroviruses like HIV tend to target gene-rich, transcriptionally active, euchromatic regions within the host’s chromosome to integrate.”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Jordan et al. 2001
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“For example, proviral integration in the transcriptionally active regions could potentially favor expression of the viral genes, whereas integration in the transcriptionally silent regions (heterochromatin) may not be in favor of viral expression and may even force the virus to stay transcriptionally silent (Jordan et al. 2001, Lewinski et al. 2006, Einkauf et al. 2022, Teixeira et al. 2024).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Jordan et al. 2001
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Metadata
- Authors
- Jordan, A., Defechereux, P., & Verdin, E.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Verdin, Eric
- Venue
- The EMBO Journal
- Published
- 2001-04-02
- Volume
- 20
- Issue
- 7
- Pages
- 1726-1738
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC145503
- OpenAlex
- W1964660012
- Cited by
- 467
- References
- 48
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 19 · 2023: 18 · 2022: 15 · 2021: 15 · 2020: 21 · 2019: 21 · 2018: 20 · 2017: 26 · 2016: 25 · 2015: 27 · 2014: 14 · 2013: 15 · 2012: 14
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Belgian American Educational Foundation
- National Institutes of Health
- National Institute of General Medical Sciences (GM51671-05A2, R01GM051671)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- 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
- Keywords
- Tat transactivation, basal transcription, chromatin environment, HIV-1 promoter, retroviral vectors, Jurkat cells, DNA methylation, histone acetylation, HIV gene expression
- MeSH terms
- Binding Sites, Cell Line, Transformed, Genetic Vectors, HeLa Cells, Humans, Hydroxamic Acids, Promoter Regions, Genetic, Tetradecanoylphorbol Acetate, Transcription, Genetic, HIV-1, Transcriptional Activation, Gene Products, tat, Genome, Human, Gene Expression Regulation, Viral, HIV Long Terminal Repeat, Virus Integration, Cyclin-Dependent Kinases, Jurkat Cells, DNA Methylation, Cyclin-Dependent Kinase 9, tat Gene Products, Human Immunodeficiency Virus, Histone Deacetylase Inhibitors
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