The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites Journal Article
| Authors: | Rivella, S.; Callegari, A. J.; May, C.; Tan, C.; Sadelain, M. |
| Article Title: | The cHS4 insulator increases the probability of retroviral expression at random chromosomal integration sites |
| Abstract: | Retroviruses are highly susceptible to transcriptional silencing and position effects impaled by chromosomal sequences at their integration site. These phenomena hamper the use of recombinant retroviruses as stable gene delivery vectors. As insulators are able to block promoter-enhancer interactions and reduce position effects in some transgenic animals, we examined the effect of an insulator on the expression and structure of randomly integrated recombinant retroviruses. We used the cHS4, element, an insulator from the chicken β-like globin gene cluster, which has been shown to reduce position effects in transgenic Drosophila. A large panel of mouse erythroleukemia cells that bear a single copy of integrated recombinant retroviruses was generated without using drag selection. We show that the cHS4 increases the probability that integrated proviruses will express and dramatically deceases the level of de novo methylation of the 5' long terminal repeat. These findings support a primary role of methylation in the silencing of retroviruses and suggest that cHS4 could be useful in gene therapy applications to overcome silencing of retroviral vectors. |
| Keywords: | controlled study; methylation; promoter region; nonhuman; flow cytometry; animal cell; mouse; animals; mice; embryo; cell line; dna methylation; transgenic animal; genetic vectors; gene therapy; dna sequence; gene silencing; virus recombinant; virus replication; moloney murine leukemia virus; transgenes; complementary dna; retrovirus; 3t3 cells; 3' untranslated regions; viral proteins; globins; virus expression; long terminal repeat; 5' untranslated regions; gene transfer techniques; enhancer region; regulatory sequences, nucleic acid; beta globin; virus dna cell dna interaction; virus integration; deoxyribonuclease i; terminal repeat sequences; priority journal; article; provirus; erythroleukemia cell |
| Journal Title: | Journal of Virology |
| Volume: | 74 |
| Issue: | 10 |
| ISSN: | 0022-538X |
| Publisher: | American Society for Microbiology |
| Date Published: | 2000-05-01 |
| Start Page: | 4679 |
| End Page: | 4687 |
| Language: | English |
| DOI: | 10.1128/jvi.74.10.4679-4687.2000 |
| PUBMED: | 10775605 |
| PROVIDER: | scopus |
| PMCID: | PMC111989 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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