The human telomeric protein TRF1 specifically recognizes nucleosomal binding sites and alters nucleosome structure.
Telomeres are dynamic nucleoprotein structures that cap the ends of eukaryotic chromosomes. In humans, the long (TTAGGG)(n) double-stranded telomeric DNA repeats are bound specifically by the two related proteins TRF1 and TRF2, and are organized in nucleosomes. Whereas the role of TRF1 and TRF2 in telomeric function has been studied extensively, little is known about the involvement of telomeric nucleosomes in telomere structures or how chromatin formation may affect binding of the TRFs. Here, we address the question of whether TRF1 is able to bind to telomeric binding sites in a nucleosomal context. We show that TRF1 is able to specifically recognize telomeric binding sites located within nucleosomes, forming a ternary complex. The formation of this complex is strongly dependent on the orientation of binding sites on the nucleosome surface, rather than on the location of the binding sites with respect to the nucleosome dyad. Strikingly, TRF1 binding causes alterations in nucleosome structure without dissociation of histone subunits. These results indicate that nucleosomes contribute to the establishment of a telomeric capping complex, whose structure and dynamics can be modulated by the binding of telomeric factors.
Galati
Alessandra
A
Dipartimento di Genetica e Biologia Molecolare, Fondazione Istituto Pasteur-Fondazione Cenci Bolognetti, Università di Roma La Sapienza, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Rossetti
Luigi
L
Pisano
Sabrina
S
Chapman
Lynda
L
Rhodes
Daniela
D
Savino
Maria
M
Cacchione
Stefano
S
D001483:Base Sequence; D001665:Binding Sites; D018983:DNA Footprinting; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D013379:Substrate Specificity; D035321:Telomeric Repeat Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D009707:Nucleosomes; D035321:Telomeric Repeat Binding Protein 1