GAA triplet-repeats cause nucleosome depletion in the human genome

分类： 生物学 >> 生物物理学 提交时间： 2016-05-11

Zhao, Hongyu Zhao, Hongyu Xing, Yongqiang Liu, Guoqing Zhao, Xiujuan Cai, Lu Chen, Ping Li, Guohong

摘要： 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 GM triplet-repeats in activated and resting CD4(+) T cells. Furthermore, the A-tract was frequently adjacent to the upstream region of GM triplet-repeats and could enhance the depletion surrounding GAA triplet-repeats. In vitro chromatin reconstitution assays with GM-containing plasmids also demonstrated that the inserted GAA triplet-repeats destabilized the ability of recombinant plasmids to assemble nucleosomes. Our results suggested that GM 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 GM triplet-repeats at the chromatin level. (C) 2015 Elsevier Inc All rights reserved.

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