title: TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization.
abstract: 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.
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy Institute Pasteur-Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galati
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy Institute Pasteur-Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Micheli
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Alicata
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Ingegnere
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy Institute Pasteur-Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cicconi
authors.affiliation: Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität, 80336 München, Germany.
authors.forename: Miriam Caroline
authors.initials: MC
authors.lastname: Pusch
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/INSERM U1081, University of Nice Sophia Antipolis, 06107 Nice, France.
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Giraud-Panis
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/INSERM U1081, University of Nice Sophia Antipolis, 06107 Nice, France Department of Medical Genetics, Hospital, CHU of Nice, 06202 Nice, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin', Sapienza University of Rome, 00185 Rome, Italy Institute Pasteur-Fondazione Cenci-Bolognetti, Sapienza University of Rome, 00185 Rome, Italy stefano.cacchione@uniroma1.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cacchione
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012091:Repetitive Sequences, Nucleic Acid; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006657:Histones; D009707:Nucleosomes; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA