Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity

We investigated the influence of telomere proximity and composition on the expression of an EGFP reporter gene in human cells. In transient transfection assays, telomeric DNA does not repress EGFP but rather slightly increases its expression. In contrast, in stable cell lines, the same reporter cons...

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Vydáno v:EMBO reports Ročník 3; číslo 11; s. 1055 - 1061
Hlavní autoři: Koering, Catherine Elaine, Pollice, Alessandra, Zibella, Maria Pia, Bauwens, Serge, Puisieux, Alain, Brunori, Michele, Brun, Christine, Martins, Luis, Sabatier, Laure, Pulitzer, John F., Gilson, Eric
Médium: Journal Article
Jazyk:angličtina
Vydáno: Chichester, UK John Wiley & Sons, Ltd 01.11.2002
Nature Publishing Group UK
Springer Nature B.V
EMBO Press
Témata:
ISSN:1469-221X, 1469-3178
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Shrnutí:We investigated the influence of telomere proximity and composition on the expression of an EGFP reporter gene in human cells. In transient transfection assays, telomeric DNA does not repress EGFP but rather slightly increases its expression. In contrast, in stable cell lines, the same reporter construct is repressed when inserted at a subtelomeric location. The telomeric repression is transiently alleviated by increasing the dosage of the TTAGGG repeat factor 1 (TRF1). Upon a prolongated treatment with trichostatin A, the derepression of the subtelomeric reporter gene correlates with the delocalization of HP1α and HP1β. In contrast, treating the cells with 5 azacytidin, a demethylating agent, or with sirtinol, an inhibitor of the Sir2 family of deacetylase, has no apparent effect on telomeric repression. Overall, position effects at human chromosome ends are dependent on a specific higher‐order organization of the telomeric chromatin. The possible involvement of HP1 isoforms is discussed.
Bibliografie:ArticleID:EMBR043
Supplementary figure 1
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PMCID: PMC1307600
ISSN:1469-221X
1469-3178
DOI:10.1093/embo-reports/kvf215