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Journal of Virology, August 2008, p. 7818-7827, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00419-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Core Element of a CpG Island Protects Avian Sarcoma and Leukosis Virus-Derived Vectors from Transcriptional Silencing{triangledown}

Filip Senigl, Jirí Plachy, and Jirí Hejnar*

Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, CZ-14220 Prague 4, Czech Republic

Received 26 February 2008/ Accepted 5 June 2008

Unmethylated CpG islands are known to keep adjacent promoters transcriptionally active. In the CpG island adjacent to the adenosine phosphoribosyltransferase gene, the protection against transcriptional silencing can be attributed to the short CpG-rich core element containing Sp1 binding sites. We report here the insertion of this CpG island core element, IE, into the long terminal repeat of a retroviral vector derived from Rous sarcoma virus, which normally suffers from progressive transcriptional silencing in mammalian cells. IE insertion into a specific position between enhancer and promoter sequences led to efficient protection of the integrated vector from silencing and gradual CpG methylation in rodent and human cells. Individual cell clones with IE-modified reporter vectors display high levels of reporter expression for a sustained period and without substantial variegation in the cell culture. The presence of Sp1 binding sites is important for the protective effect of IE, but at least some part of the entire antisilencing capacity is maintained in IE with mutated Sp1 sites. We suggest that this strategy of antisilencing protection by the CpG island core element may prove generally useful in retroviral vectors.

* Corresponding author. Mailing address: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ-14220 Prague 4, Czech Republic. Phone: (420) 296 443 443. Fax: (420) 224 310 955. E-mail: hejnar{at}img.cas.cz

{triangledown} Published ahead of print on 11 June 2008.

Journal of Virology, August 2008, p. 7818-7827, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00419-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schon, U., Diem, O., Leitner, L., Gunzburg, W. H., Mager, D. L., Salmons, B., Leib-Mosch, C. (2009). Human Endogenous Retroviral Long Terminal Repeat Sequences as Cell Type-Specific Promoters in Retroviral Vectors. J. Virol. 83: 12643-12650 [Abstract] [Full Text]  


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