Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation.

Verdin, Eric; Paras, P; Lint, Carine Van

doi:10.1002/j.1460-2075.1993.tb05994.x

Cited by 459 publications

(554 citation statements)

References 81 publications

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“…In a similar manner, induction of the MMTV promoter by the glucocorticoid receptor results in the selective remodeling of the nucleosome spanning the glucocorticoid receptor binding sites (17)(18)(19). By comparison, the HIV promoter is nucleosome free, but nucleosomes positioned downstream of the transcription start site undergo remodeling upon T cell activation (20,21). These studies clearly establish that alterations in chromatin structure play an important role in the regulation of inducible transcription in eukaryotes.…”

mentioning

confidence: 67%

Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene

Rao¹,

Procko²,

Shannon³

2001

The Journal of Immunology

183

222

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The structure of chromatin and its remodeling following activation are important aspects of the control of inducible gene transcription. The IL-2 gene is induced in a cell specific-manner in T cells following an antigenic stimulus. We show, using a novel real-time PCR assay, that significant chromatin remodeling of the IL-2 proximal promoter region occurred upon stimulation of both the murine EL-4 T cell line and primary CD4+ T cells. Chromatin remodeling appears to be limited to the first 300 bp of the proximal promoter region as measured by micrococcal nuclease and restriction enzyme accessibility. Time course studies indicated that chromatin remodeling was observed at 1.5 h postinduction and was maintained for up to 16 h. The remodeling is reversible upon removal of the stimulus. The region immediately upstream from the transcription start site, however, remains accessible for up to 16 h. Upon restimulation, remodeling occurs much more rapidly, consistent with a more rapid rise in IL-2 mRNA levels. Using a number of pharmacological inhibitors we show that remodeling is dependent on the presence of specific transcription factors, but not on the modification of histones. The development of this novel chromatin accessibility assay based on real-time PCR has allowed rapid, sensitive, and quantitative measurements on the IL-2 gene following cellular activation in both T cell lines and primary cells.

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mentioning

confidence: 67%

Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene

Rao¹,

Procko²,

Shannon³

2001

The Journal of Immunology

183

222

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“…Earlier studies demonstrate that nucleosomes are precisely positioned at the HIV-1 LTR, and their organization is conserved (71)(72)(73). We expect that FACT proteins may impose a similar effect on the HIV-1 LTR chromatin across various cell models of HIV-1 latency.…”

Section: Supt16h and Ssrp1 Regulatementioning

confidence: 82%

FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency

Huang

Santoso

Power

et al. 2015

Journal of Biological Chemistry

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Background: FACT proteins SUPT16H and SSRP1 are identified as host factors that restrict HIV-1 replication. Results: Biochemical and genetic evidences that SUPT16H and SSRP1 affect HIV-1/HTLV-1 transcription and latency are provided. Conclusion: SUPT16H and SSRP1 suppress transcription of HIV-1/HTLV-1, and their presence may promote HIV-1 latency. Significance: Identification of host factors necessary for HIV-1 latency is critical, which may benefit the development of novel HIV-1 latency-reversing agents.

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“…Alternatively, preactivation latency has also been described, where HIV-1 DNA can be integrated into quiescent rCD4 cells via interactions of chemokines with CCR7, CXCR3, and CCR6 in the absence of productive infection (21). Independently of whether productive infection has occurred, the G 0 resting state in rCD4 cells contributes to the inhibition of HIV-1 transcription and translation through a variety of mechanisms, including the sequestration of transcription factors NF-κB and NFAT (22,23); association of P-TEFb with the inhibitory 7SK snRNA complex (24,25); and association of the BAF complex and histone deacetylases with the HIV long terminal repeat (26,27). In addition to transcriptional blocks, posttranscriptional nuclear sequestration of the spliced tat and rev HIV-1 mRNAs in latently infected rCD4 cells prevent productive infection (28).…”

Section: Discussionmentioning

confidence: 99%

Quantification of HIV-1 latency reversal in resting CD4 ⁺ T cells from patients on suppressive antiretroviral therapy

Cillo

Sobolewski

Bosch

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

213

218

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Reversal of proviral latency is being pursued as a curative strategy for HIV-1 infection. Recent clinical studies of in vivo administration of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA; vorinostat) show increases in unspliced cellular HIV-1 RNA levels in resting CD4 + T cells. A critical unknown, however, is the proportion of latent proviruses that can be transcriptionally reactivated by SAHA or T-cell activation. In this study, we quantified the fraction of HIV-1 proviruses in resting CD4 + T cells from patients on suppressive antiretroviral therapy that were reactivated ex vivo with SAHA or antibodies to CD3/CD28. At concentrations of SAHA achieved clinically, only 0.079% of proviruses in resting CD4 + T cells were reactivated to produce virions, compared with 1.5% of proviruses in cells treated with anti-CD3/CD28 antibodies after correcting for spontaneous virion production in the medium control. A significant positive correlation (ρ = 0.67, P < 0.001) was found between levels of virions in the supernatant and unspliced cellular HIV-1 RNA following anti-CD3/CD28 treatment, but not following SAHA treatment (ρ = 0.21, P = 0.99). These results reveal that the majority of HIV-1 proviruses are not reactivated by current therapeutic approaches and that more effective means of reversing proviral latency will likely be required to deplete HIV-1 reservoirs.HIV-1 persistence | HIV-1 eradication | HIV-1 cure | fractional provirus expression A ntiretroviral therapy (ART) for HIV-1 infection suppresses viral replication but is not curative. Assays of infectious virus recovery from quiescent CD4 + T cells isolated from patients on ART have revealed the existence of a reservoir of latent, replication competent HIV-1 with a half-life of 44 mo (1-4). In addition, low-level plasma viremia persists indefinitely on ART (5, 6), and the level of virus in plasma rebounds following cessation of ART (7,8). New therapeutic approaches are required to eliminate both persistent low-level viremia and the latent proviral reservoir. A "kick and kill" approach has been proposed in which latency reversing agents, administered in conjunction with ART, will "kick" proviruses out of latency, followed by a "kill" of the infected cells through viral cytopathic effects or immune-mediated cytotoxicity.Histone deacetylase inhibitors (HDACi) have been proposed as latency reversing agents, and single-dose or multidose administration of suberoylanilide hydroxamic acid (SAHA; vorinostat) in vivo was shown to increase expression of unspliced cellular HIV-1 RNA in resting CD4 + T (rCD4) cells in patients on suppressive ART (9, 10). Although three-to fivefold increases in cellular HIV-1 RNA were observed (9), the fraction of latent HIV-1 proviruses that were reactivated by SAHA was not quantified. It is possible that SAHA transcriptionally reactivated many latent proviruses, or alternatively reactivated only a minority of latent proviruses. These two alternatives have very different implications in terms of the impact SAHA coul...

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Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation.

Cited by 459 publications

References 81 publications

Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene

Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene

FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency

Quantification of HIV-1 latency reversal in resting CD4 ⁺ T cells from patients on suppressive antiretroviral therapy

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Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation.

Cited by 459 publications

References 81 publications

Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene

Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene

FACT Proteins, SUPT16H and SSRP1, Are Transcriptional Suppressors of HIV-1 and HTLV-1 That Facilitate Viral Latency

Quantification of HIV-1 latency reversal in resting CD4 + T cells from patients on suppressive antiretroviral therapy

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Product

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Quantification of HIV-1 latency reversal in resting CD4 ⁺ T cells from patients on suppressive antiretroviral therapy