Genome-Wide Analysis of Chromosomal Features Repressing Human Immunodeficiency Virus Transcription

Lewinski, Mary K.; Bisgrove, Dwayne A.; Shinn, Paul; Chen, Hongwu; Hoffmann, Christian; Hannenhalli, Sridhar; Verdin, Eric; Berry, Charles C.; Ecker, Joseph R.; Bushman, Frederic D.

doi:10.1128/jvi.79.11.6610-6619.2005

Cited by 244 publications

(269 citation statements)

References 49 publications

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“…Hence, repressive chromatin domains in tight conjunction with the nuclear lamina are not favorable sites for HIV-1 integration. This is consistent with the observation that HIV-1 integrated preferentially within active genes 20,22 and active genes are also enriched outside LADs. 19 Since, the analysis in Figure 1B was conducted on different human cell types (fibroblasts and lymphocytes) that may differ in the organization of the nucleus, it will be important to confirm these data in the same cellular background, possibly from latently infected patients.…”

supporting

confidence: 80%

“…Therefore we took advantage of two libraries of integration sites generated in the laboratory of Frederic D. Bushman. 20 One set of integration sites was derived from cells that expressed the provirus constitutively, the other from cells that expressed the provirus poorly but could be reactivated by TNFα, an agent that is known to activate LTR transcription. The latter represent latently infected cells and are particularly relevant to HIV-1 persistence during antiviral therapy.…”

mentioning

confidence: 99%

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Nuclear positional control of HIV transcription in 4D

Marcello¹,

Dhir²,

Dieudonné³

2010

Nucleus

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supporting

confidence: 80%

mentioning

confidence: 99%

Nuclear positional control of HIV transcription in 4D

Marcello¹,

Dhir²,

Dieudonné³

2010

Nucleus

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“…For this, we selected GFP-negative cells in the presence of Dox to a degree of purity of 99.2% and subjected the resulting population to various drug treatments. We first observed that tumor necrosis factor ␣ did not increase the percentage of GFPpositive cells (not illustrated), in striking contrast with what was previously observed in T lymphoid Jurkat cells transduced with a vector expressing GFP from the HIV long terminal repeat (11). We then treated the cells with TSA and 5-aza-dC, alone or in combination, to relieve possible silencing by histone deacetylation and/or DNA methylation (Fig.…”

Section: Resultscontrasting

confidence: 47%

KRAB Can Repress Lentivirus Proviral Transcription Independently of Integration Site

Bulliard

Wiznerowicz

Barde

et al. 2006

Journal of Biological Chemistry

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The KRAB transcriptional repressor domain, commonly found in zinc finger proteins, acts by inducing the formation of heterochromatin. We previously exploited this property to achieve drug-regulated transgenesis and knock down by combining doxycycline-controllable KRAB-containing fusion proteins and lentiviral vectors. Here, we asked whether KRAB-induced repression is widespread or limited to specific regions of the genome. For this, we transduced cells with a lentiviral vector expressing a target reporter and a KRAB-containing transcriptional repressor from a bicistronic mRNA. We found that ϳ1.4% of the resulting proviruses escaped repression. However, this phenotype could be reverted by expressing the KRAB-containing protein in trans. Accordingly, the irrepressible proviruses all contained, in the DNA sequence encoding the KRAB-containing effector or its upstream internal ribosomal entry site, mutations or deletions likely resulting from errors or recombination during reverse transcription. These results indicate that KRABinduced transcriptional repression is robust and active over a variety of genomic contexts that include at least the wide range of sites targeted by lentiviral integration.

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“…Integration sites were mapped onto the human genome sequence (Fig. 3A) and the distribution compared with human genomic features and previously determined HIV integration sites (15)(16)(17)(18). Studies have shown that integration by HIV or HIV-based vectors was favored in gene-rich regions, and this trend was also seen for the antisense env vector ( Fig.…”

Section: Resultsmentioning

confidence: 99%