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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Published in:EMBO reports Vol. 3; no. 11; pp. 1055 - 1061
Main Authors: 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
Format: Journal Article
Language:English
Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2002
Nature Publishing Group UK
Springer Nature B.V
EMBO Press
Subjects:
Biochemistry, Molecular Biology
Bioinformatics
Chromatin - metabolism
Chromosomes, Human - metabolism
Computer Science
Gene Expression Regulation
Gene Silencing
Genes, Reporter
Humans
Life Sciences
Molecular biology
Scientific Report
Telomere - metabolism
Telomeric Repeat Binding Protein 1 - genetics
Telomeric Repeat Binding Protein 1 - metabolism
Tumor Cells, Cultured
ISSN:1469-221X, 1469-3178
Online Access:Get full text
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Summary: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.
Bibliography:ArticleID:EMBR043
Supplementary figure 1
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PMCID: PMC1307600
ISSN:1469-221X
1469-3178
DOI:10.1093/embo-reports/kvf215