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PubMed

Záznam pochází z PubMed

Proviruses selected for high and stable expression of transduced genes accumulate in broadly transcribed genome areas

Journal of virology. 2010 May ; 84 (9) : 4204-11. [epub] 20100210

J Virol
ISSN 1098-5514 | 0022-538X
Zdroj

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz https://www.medvik.cz/link/pmid20147411

Online Plný text

PubMed 20147411
PubMed Central PMC2863777
DOI 10.1128/jvi.02511-09
PII: JVI.02511-09
Knihovny.cz E-zdroje

MeSH
chromozomy virologie MeSH
exprese genu MeSH
genetická terapie metody MeSH
genetické vektory MeSH
integrace viru * MeSH
kur domácí MeSH
proviry genetika fyziologie MeSH
ptačí sarkom virologie MeSH
viry ptačího sarkomu genetika fyziologie MeSH
zvířata MeSH
Check Tag
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Retroviruses and retrovirus-derived vectors integrate nonrandomly into the genomes of host cells with specific preferences for transcribed genes, gene-rich regions, and CpG islands. However, the genomic features that influence the transcriptional activities of integrated retroviruses or retroviral vectors are poorly understood. We report here the cloning and characterization of avian sarcoma virus integration sites from chicken tumors. Growing progressively, dependent on high and stable expression of the transduced v-src oncogene, these tumors represent clonal expansions of cells bearing transcriptionally active replication-defective proviruses. Therefore, integration sites in our study distinguished genomic loci favorable for the expression of integrated retroviruses and gene transfer vectors. Analysis of integration sites from avian sarcoma virus-induced tumors showed strikingly nonrandom distribution, with proviruses found prevalently within or close to transcription units, particularly in genes broadly expressed in multiple tissues but not in tissue-specifically expressed genes. We infer that proviruses integrated in these genomic areas efficiently avoid transcriptional silencing and remain active for a long time during the growth of tumors. Defining the differences between unselected retroviral integration sites and sites selected for long-terminal-repeat-driven gene expression is relevant for retrovirus-mediated gene transfer and has ramifications for gene therapy.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Videnska 1083 CZ 14220 Prague 4 Czech Republic

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