Specific interactions between nucleosomes and human telomeric proteins TRF1 and TRF2.

Telomeric structure is not yet completely understood. Several proteins have been identified that associate with human telomeres, such as hTRF1 and hTRF2 which bind to duplex telomeric repeats and Pot1 which binds to single-stranded overhangs. Indeed, most human double-stranded telomeric DNA is organized into tightly spaced nucleosomes. Nucleosomes formed on telomeric sequences are less stable than bulk nucleosomes and occupy multiple positions spaced every telomere repeat, suggesting a high intrinsic mobility of telomeric nucleosomes. Little is known about the involvement of telomeric nucleosomes in the establishment of higher order telomere structures. Moreover, in a dynamic view of telomere structure an understanding of how specific telomeric proteins interact and/or compete with nucleosome formation deserves further attention. By band shift assay and footprinting analyses we found that hTRF proteins are able to specifically recognize their binding sites in a nucleosomal context. Experiments are in progress to examine if hTRF1 and hTRF2 binding could induce nucleosome shifting or dissociation, or the formation of nucleosome-nucleosome bridges, by using a model system to study nucleosome mobility and taking advantage of AFM imaging.