TRF2 controls telomeric nucleosome organization in a cell cycle phase-dependent manner

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 nucleosomes are present in mammalian telomeric chromatin, how they interplay with telomere-specific factors in telomere organization is still unclear. In the current study, we find in human cells that the density of telomeric nucleosomes is inversely proportional to the dosage of TRF2 at telomeres. This effect is not observed in the G1 phase of the cell cycle but appears coincident of late or post-replicative events. Moreover, we show that TRF2 increases internucleosomal distance at telomeres both in vitro and in vivo. We conclude that TRF2 negatively regulates the number of nucleosomes at telomeres by a cell cycle-dependent mechanism that alters inter-nucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization.