TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization

The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-...

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Bibliographic Details
Published in:Nucleic acids research 2015-07, Vol.43 (12), p.5824-5837
Main Authors: Galati, Alessandra, Micheli, Emanuela, Alicata, Claudia, Ingegnere, Tiziano, Cicconi, Alessandro, Pusch, Miriam Caroline, Giraud-Panis, Marie-Josèphe, Gilson, Eric, Cacchione, Stefano
Format: Article
Language:English
Subjects:
Binding Sites
Biochemistry, Molecular Biology
DNA - metabolism
Gene regulation, Chromatin and Epigenetics
Genomics
Histones - metabolism
Life Sciences
Nucleosomes - chemistry
Nucleosomes - metabolism
Protein Binding
Protein Structure, Tertiary
Repetitive Sequences, Nucleic Acid
Telomere - chemistry
Telomere - metabolism
Telomeric Repeat Binding Protein 1 - chemistry
Telomeric Repeat Binding Protein 1 - metabolism
Telomeric Repeat Binding Protein 2 - chemistry
Telomeric Repeat Binding Protein 2 - metabolism
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Summary:The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkv507