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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| Vydané v: | EMBO reports Ročník 3; číslo 11; s. 1055 - 1061 |
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| Hlavní autori: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Chichester, UK
John Wiley & Sons, Ltd
01.11.2002
Nature Publishing Group UK Springer Nature B.V EMBO Press |
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| ISSN: | 1469-221X, 1469-3178 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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 HP1[alpha] and HP1[beta]. 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. 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 HP1alpha and HP1beta. 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. 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. 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. 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 HP1alpha and HP1beta. 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.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 HP1alpha and HP1beta. 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. |
| Author | Sabatier, Laure Gilson, Eric Zibella, Maria Pia Koering, Catherine Elaine Pollice, Alessandra Bauwens, Serge Brun, Christine Martins, Luis Brunori, Michele Puisieux, Alain Pulitzer, John F. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12393752$$D View this record in MEDLINE/PubMed https://amu.hal.science/hal-01596225$$DView record in HAL |
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| Copyright | European Molecular Biology Organization 2002 Copyright © 2002 European Molecular Biology Organization Copyright Oxford University Press(England) Nov 15, 2002 Distributed under a Creative Commons Attribution 4.0 International License Copyright © 2002, European Molecular Biology Organization 2002 |
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| PublicationCentury | 2000 |
| PublicationDate | November 2002 |
| PublicationDateYYYYMMDD | 2002-11-01 |
| PublicationDate_xml | – month: 11 year: 2002 text: November 2002 |
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| PublicationPlace | Chichester, UK |
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| PublicationTitle | EMBO reports |
| PublicationTitleAbbrev | EMBO Rep |
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| PublicationYear | 2002 |
| Publisher | John Wiley & Sons, Ltd Nature Publishing Group UK Springer Nature B.V EMBO Press |
| Publisher_xml | – name: John Wiley & Sons, Ltd – name: Nature Publishing Group UK – name: Springer Nature B.V – name: EMBO Press |
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| References_xml | – reference: Harrison, J.J., Anisowicz, A., Gadi, I.K., Raffeld, M. and Sager, R. (1983) Azacytidine-induced tumorigenesis of CHEF/18 cells: correlated DNA methylation and chromosome changes. Proc. Natl Acad. Sci. USA, 80, 6606-6610. – reference: Chong, L., van Steensel, B., Broccoli, D., Erdjument-Bromage, H., Hanish, J., Tempst, P. and de Lange, T. (1995) A human telomeric protein. Science, 270, 1663-1667. – reference: Fourel, G., Revardel, E., Koering, C.E. and Gilson, E. (1999) Cohabitation of insulators and silencing elements in yeast subtelomeric regions. EMBO J., 18, 2522-2537. – reference: Baur, J.A., Zou, Y., Shay, J.W. and Wright, W.E. (2001) Telomere position effect in human cells. Science, 292, 2075-2077. – reference: Lundblad, V. (2000) DNA ends: maintenance of chromosome termini versus repair of double strand breaks. Mutat. Res., 451, 227-240. – reference: Gottschling, D.E., Aparicio, O.M., Billington, B.L. and Zakian, V.A. 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| Snippet | We investigated the influence of telomere proximity and composition on the expression of an
EGFP
reporter gene in human cells. In transient transfection... We investigated the influence of telomere proximity and composition on the expression of an EGFP reporter gene in human cells. In transient transfection... |
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| SubjectTerms | 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 |
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| Title | Human telomeric position effect is determined by chromosomal context and telomeric chromatin integrity |
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