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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Veröffentlicht in:	EMBO reports Jg. 3; H. 11; S. 1055 - 1061
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	Chichester, UK John Wiley & Sons, Ltd 01.11.2002 Nature Publishing Group UK Springer Nature B.V EMBO Press
Schlagworte:	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-Zugang:	Volltext
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Zusammenfassung:	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.
Bibliographie:	ArticleID:EMBR043 Supplementary figure 1 istex:1500E0C37C56068C560B099A656E42062774E8DF ark:/67375/WNG-JD4R6VWM-C ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC1307600
ISSN:	1469-221X 1469-3178
DOI:	10.1093/embo-reports/kvf215