Mammalian telomeres consist of the tandemly arranged DNA sequence repeats TTAGGG that act as a platform for the recruitment of the capping structure at the end of the linear chromosomes, which protect their ends from incorrect DNA repair and degradation. In humans, this consists of the six-protein Shelterin complex as well as nucleosomes that package 5–15 kbp of telomeric DNA into chromatin. Aberrant regulation of telomeres has been linked with cancer development and ageing-associated pathologies. However, almost nothing was known about the structure of telomeric chromatin at the molecular level. Recently (Soman et al, Nature, 699, 1048, 2022), we characterized telomeric chromatin fibres with EM and single-molecule magnetic tweezers. We determined the Cryo-EM structure of the condensed telomeric tetra-nucleosome chromatin fibre, which revealed a novel columnar architecture. The structure of the di-nucleosome unit at 3.9 Å resolution displays about 130 bp DNA wound in a continuous super-helix around the closely stacked histone octamers. We identified a distinct open conformation in which one nucleosome is flipped out from its stacked position, with the two NCP discs perpendicular to each other and accessible to chromatin modifiers. I will review this novel columnar packaging of telomeric chromatin in light of new recent results and discuss its implications for telomere maintenance as well as for chromatin structure in general.

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