GAA triplet-repeats cause nucleosome depletion in the human genome

• There is a nucleosome depleted region in the vicinity of GAA triplet-repeats in activated and resting CD4+ T cells.
• A-tracts are frequently adjacent to the upstream regions and can enhance the nucleosome depletion on GAA triplet-repeats.
• GAA triplet-repeats inserts destabilized the ability of recombinant plasmids to assemble nucleosome in vitro.

Although there have been many investigations into how trinucleotide repeats affect nucleosome formation and local chromatin structure, the nucleosome positioning of GAA triplet-repeats in the human genome has remained elusive. In this work, the nucleosome occupancy around GAA triplet-repeats across the human genome was computed statistically. The results showed a nucleosome-depleted region in the vicinity of GAA triplet-repeats in activated and resting CD4+ T cells. Furthermore, the A-tract was frequently adjacent to the upstream region of GAA triplet-repeats and could enhance the depletion surrounding GAA triplet-repeats. In vitro chromatin reconstitution assays with GAA-containing plasmids also demonstrated that the inserted GAA triplet-repeats destabilized the ability of recombinant plasmids to assemble nucleosomes. Our results suggested that GAA triplet-repeats have lower affinity to histones and can change local nucleosome positioning. These findings may be helpful for understanding the mechanism of Friedreich's ataxia, which is associated with GAA triplet-repeats at the chromatin level.