The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Closed Chromatin Architecture Is Induced by an RNA Duplex Targeting the HIV-1 Promoter Region
Open accessAbstract
In some mammalian systems small interfering RNAs (siRNA) targeting homologous sequences in promoter regions of genes induce transcriptional gene silencing (TGS). We have previously reported the induction of TGS by an siRNA (prom-A siRNA) targeting the tandem NF-kappaB-binding motifs within the human immunodeficiency virus, type 1 (HIV-1), promoter region. Here we report that induction of TGS by prom-A siRNA is accompanied by immediate and sustained local recruitment of Argonaute-1 (Ago1), histone deacetylase-1 (HDAC1), and induction of dimethylation of histone 3 at lysine 9 (H3K9me2), processes known to be associated with transcriptional silencing. Elevated levels of H3K9me2 and HDAC1 spread upstream of the target sequence, and elevated H3K9me2 levels also spread downstream into the coding region. Moreover, this siRNA induces an immediate change in DNA accessibility to restriction enzyme digestion in the region of the transcription initiation site of the HIV-1. This change in accessibility is because of the relocation of a nucleosome known to be associated with this region of the integrated pro-virus. Although there is a theoretical possibility that the observed viral suppression could be mediated by the PTGS mechanism with this siRNA acting at the 3 (R)-long term repeat of the virus, we demonstrate that this siRNA, and three other U3 targeted siRNAs, are inefficient inducers of PTGS. These data strongly suggest that siRNA targeting the promoter region acts predominantly at a site within the 5 (R)-long term repeat of HIV to induce transcriptional silencing and alterations to chromatin structure of the HIV promoter region that extend well beyond the immediate siRNA target site. These induced changes are consistent with those described in latent HIV-1 infection.
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“The first anti-HIV-1, siPromA, was first identified in 2005 [309], and targeted the unique and highly conserved NK-κB transcription factor sites in the HIV-1 promoter to induce potent epigenetic silencing [70,310,311,312].”
From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [310]
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1 retracted
Pulukuri, S. M. K., & Rao, J. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0751 · Cited by 62
RetractedAdachi, A., Gendelman, H. E., Koenig, S., Folks, T. M., Willey, R. L., Rabson, A. B., & Martín, M. Á. (1986) · Journal of Virology · doi:10.1128/jvi.59.2.284-291.1986 · Cited by 2,805
The Polycomb group protein EZH2 directly controls DNA methylation
Viré, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., et al. (2006) · Nature · doi:10.1038/nature04431 · Cited by 2,204
Rational siRNA design for RNA interference
Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S., & Khvorova, A. (2004) · Nature Biotechnology · doi:10.1038/nbt936 · Cited by 2,094
Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly
Nakayama, J.-I., Rice, J. C., Strahl, B. D., Allis, C. D., & Grewal, S. I. S. (2001) · Science · doi:10.1126/science.1060118 · Cited by 1,739
Siliciano, J. D., Kajdas, J., Finzi, D., Quinn, T. C., Chadwick, K., Margolick, J. B., Kovacs, C., Gange, S. J., & Siliciano, R. F. (2003) · Nature Medicine · doi:10.1038/nm880 · Cited by 1,703
Genetic and Functional Diversification of Small RNA Pathways in Plants
Xie, Z., Johansen, L. K., Gustafson, A. M., Kasschau, K. D., Lellis, A. D., Zilberman, D., Jacobsen, S. E., & Carrington, J. C. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020104 · Cited by 1,569
Argonaute proteins: key players in RNA silencing
Hutvágner, G., & Simard, M. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2321 · Cited by 1,386
Carrozza, M. J., Li, B., Florens, L. A., Suganuma, T., Swanson, S. K., Lee, K. K., Shia, W.-J., Anderson, S., Yates, J. R., Washburn, M. P., et al. (2005) · Cell · doi:10.1016/j.cell.2005.10.023 · Cited by 1,338
P bodies and the control of mRNA translation and degradation
Parker, R., & Sheth, U. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.02.011 · Cited by 1,335
Flagged first, then by citations
Research works printed but not linked: 2
- Suzuki, 2005, J. RNAi Gene Silencing, 1, 66
- Hutvagner, 2008, Nat. Rev. Mol. Cell Biol., 105, 512
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(2013) · Elsevier eBooks · doi:10.1016/b978-0-12-416570-0.00043-3
Palanichamy, J. K., Mehndiratta, M., Bhagat, M., Ramalingam, P., Das, B., Das, P., Sinha, S., & Chattopadhyay, P. (2023) · doi:10.1158/1535-7163.c.6531921.v1
Palanichamy, J. K., Mehndiratta, M., Bhagat, M., Ramalingam, P., Das, B., Das, P., Sinha, S., & Chattopadhyay, P. (2023) · doi:10.1158/1535-7163.c.6531921
Gene therapy to cure HIV infection
Goguen, R. P., Chen, M. J., Dunkley, O. R. S., Gatignol, A., & Scarborough, R. J. (2023) · Virologie · doi:10.1684/vir.2023.1021 · Cited by 1
Mkhize, Z. (2023) · ResearchSpace (University of KwaZulu-Natal) · doi:10.29086/10413/23002
Argonaute 1 contributes to the transcriptional silencing of HIV-1
Goudey, S., Said, M. A., Desforges, J., Marie, S., Morel, M., Berlioz‐Torrent, C., Margottin-Goguet, F., Emiliani, S., Matkovic, R., & Gallois‐Montbrun, S. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.110612
Current treatment of HIV and prospects for cure
Kŕause, W. (2025) · Exploration of Medicine · doi:10.37349/emed.2025.1001364
Kia, P., Kankaka, E. N., Kankundiye, P., Tongo, M., Nabatanzi, R., Mahmoudi, T., & Nakanjako, D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1918867
Metadata
- Authors
- Suzuki, K., Juelich, T., Lim, H., Ishida, T., Watanebe, T., Cooper, D. A., Rao, S., & Kelleher, A. D.
- Affiliations
- St Vincent's Hospital Sydney (AU)
- UNSW Sydney (AU)
- The University of Tokyo (JP)
- Corresponding author
- Suzuki, Kazuo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 283
- Issue
- 34
- Pages
- 23353-23363
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2516975
- OpenAlex
- W1993695454
- Cited by
- 108
- References
- 79
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 10 · 2014: 12 · 2013: 9 · 2012: 5
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- National Institutes of Health (pNL4-3)
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- HIV-1 promoter, transcriptional silencing, siRNA, RNA duplex, AGO1, HDAC1, H3K9 dimethylation, chromatin structure, DNA accessibility, long terminal repeat, HIV latency
- MeSH terms
- Binding Sites, Chromatin, HeLa Cells, HIV, Humans, Models, Biological, Nucleosomes, Promoter Regions, Genetic, RNA, Transcription, Genetic, Transfection, HIV-1, NF-kappa B, Gene Silencing, RNA, Small Interfering
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