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PMID:22536324

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Citation

Galati, A, Magdinier, F, Colasanti, V, Bauwens, S, Pinte, S, Ricordy, R, Giraud-Panis, MJ, Pusch, MC, Savino, M, Cacchione, S and Gilson, E (2012) TRF2 controls telomeric nucleosome organization in a cell cycle phase-dependent manner. PLoS ONE 7:e34386

Abstract

Mammalian telomeres stabilize chromosome ends as a result of their assembly into a peculiar form of chromatin comprising a complex of non-histone proteins named shelterin. TRF2, one of the shelterin components, binds to the duplex part of telomeric DNA and is essential to fold the telomeric chromatin into a protective cap. Although most of the human telomeric DNA is organized into tightly spaced nucleosomes, their role in telomere protection and how they interplay with telomere-specific factors in telomere organization is still unclear. In this study we investigated whether TRF2 can regulate nucleosome assembly at telomeres.By means of chromatin immunoprecipitation (ChIP) and Micrococcal Nuclease (MNase) mapping assay, we found that the density of telomeric nucleosomes in human cells was inversely proportional to the dosage of TRF2 at telomeres. This effect was not observed in the G1 phase of the cell cycle but appeared coincident of late or post-replicative events. Moreover, we showed that TRF2 overexpression altered nucleosome spacing at telomeres increasing internucleosomal distance. By means of an in vitro nucleosome assembly system containing purified histones and remodeling factors, we reproduced the short nucleosome spacing found in telomeric chromatin. Importantly, when in vitro assembly was performed in the presence of purified TRF2, nucleosome spacing on a telomeric DNA template increased, in agreement with in vivo MNase mapping.Our results demonstrate that TRF2 negatively regulates the number of nucleosomes at human telomeres by a cell cycle-dependent mechanism that alters internucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization.

Links

PubMed PMC3335031 Online version:10.1371/journal.pone.0034386

Keywords

Cell Cycle Checkpoints; Cell Line, Tumor; Chromatin/metabolism; Chromatin Assembly and Disassembly; Chromatin Immunoprecipitation; Gene Expression; Humans; Nucleosomes/metabolism; Protein Binding; Telomere/metabolism; Telomeric Repeat Binding Protein 2/genetics; Telomeric Repeat Binding Protein 2/metabolism; Telomeric Repeat Binding Protein 2/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TERF2

GO:0032204: regulation of telomere maintenance

ECO:0000315:

P

Fig. 1

complete
CACAO 9092

HUMAN:TERF2

involved_in

GO:0032204: regulation of telomere maintenance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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