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DNA methyltransferases control telomere length and telomere recombination in mammalian cells

Gonzalo, Susana, Jaco, Isabel, Fraga, Mario F., Chen, Taiping, Li, En, Esteller, Manel, Blasco, María A.·2006·Nature Cell Biology
DOI 10.1038/ncb1386
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Abstract

Here, we describe a role for mammalian DNA methyltransferases (DNMTs) in telomere length control. Mouse embryonic stem (ES) cells genetically deficient for DNMT1, or both DNMT3a and DNMT3b have dramatically elongated telomeres compared with wild-type controls. Mammalian telomere repeats (TTAGGG) lack the canonical CpG methylation site. However, we demonstrate that mouse subtelomeric regions are heavily methylated, and that this modification is decreased in DNMT-deficient cells. We show that other heterochromatic marks, such as histone 3 Lys 9 (H3K9) and histone 4 Lys 20 (H4K20) trimethylation, remain at both subtelomeric and telomeric regions in these cells. Lack of DNMTs also resulted in increased telomeric recombination as indicated by sister-chromatid exchanges involving telomeric sequences, and by the presence of 'alternative lengthening of telomeres' (ALT)-associated promyelocytic leukaemia (PML) bodies (APBs). This increased telomeric recombination may lead to telomere-length changes, although our results do not exclude a potential involvement of telomerase and telomere-binding proteins in the aberrant telomere elongation observed in DNMT-deficient cells. Together, these results demonstrate a previously unappreciated role for DNA methylation in maintaining telomere integrity.

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Crossref · 10.1038/ncb1386

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  • Mammalian telomeric repeats are enriched for these chromatin modifications, indicating that chromosome ends are assembled into heterochromatin domains.

    “Mammalian telomeric repeats are also enriched for these chromatin modifications, indicating that chromosome ends are assembled into heterochromatin domains (Gonzalo et al., 2006).”

    From The Hallmarks of Aging (2013) · cites this paper as Gonzalo et al., 2006

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Research works printed but not linked: 27

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Metadata

Authors
Gonzalo, S., Jaco, I., Fraga, M. F., Chen, T., Li, E., Esteller, M., & Blasco, M. A.
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2006-03-26
Volume
8
Issue
4
Pages
416-424
ISSN
  • 1465-7392
  • 1476-4679
DOI
10.1038/ncb1386
Cited by
544
References
6
Language
en
Licence
www.springer.com/tdm (tdm)

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