Accumulation of long-term transcriptionally active integrated retroviral vectors in active promoters and enhancers

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00487081" target="_blank" >RIV/68378050:_____/17:00487081 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1093/nar/gkx889" target="_blank" >http://dx.doi.org/10.1093/nar/gkx889</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkx889" target="_blank" >10.1093/nar/gkx889</a>

Result language

angličtina

Original language name

Accumulation of long-term transcriptionally active integrated retroviral vectors in active promoters and enhancers

Original language description

Most retroviruses preferentially integrate into certain genomic locations and, as a result, their genome-wide integration patterns are non-random. We investigate the epigenetic landscape of integrated retroviral vectors and correlate it with the long-term stability of proviral transcription. Retroviral vectors derived from the avian sarcoma/leukosis virus expressing the GFP reporter were used to transduce the human myeloid lymphoblastoma cell line K562. Because of efficient silencing of avian retrovirus in mammalian cells, only similar to 3% of established clones displayed stable proviral expression. We analyzed the vector integration sites in non-selected cells and in clones selected for the GFP expression. This selection led to overrepresentation of proviruses integrated in active transcription units, with particular accumulation in promoter-proximal areas. In parallel, we investigated the integration of vectors equipped with an anti-silencing CpG island core sequence. Such modification increased the frequency of stably expressing proviruses by one order. The modified vectors are also overrepresented in active transcription units, but stably expressed in distal parts of transcriptional units further away from promoters with marked accumulation in enhancers. These results suggest that integrated retroviruses subject to gradual epigenetic silencing during long-term cultivation. Among most genomic compartments, however, active promoters and enhancers protect the adjacent retroviruses from transcriptional silencing.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10607 - Virology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

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Volume of the periodical

45

Issue of the periodical within the volume

22

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

12752-12765

UT code for WoS article

000419064400019

EID of the result in the Scopus database

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