title: GAA triplet-repeats cause nucleosome depletion in the human genome.
abstract: 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.
authors.affiliation: School of Physical Science and Technology, Inner Mongolia University, Hohhot 010021, China; School of Mathematics, Physics and Biological Engineering, Inner Mongolia University of Science and Technology, Baotou 014010, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Mathematics, Physics and Biological Engineering, Inner Mongolia University of Science and Technology, Baotou 014010, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Xing
authors.affiliation: School of Mathematics, Physics and Biological Engineering, Inner Mongolia University of Science and Technology, Baotou 014010, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Liu
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: School of Mathematics, Physics and Biological Engineering, Inner Mongolia University of Science and Technology, Baotou 014010, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liguohong@sun5.ibp.ac.cn.
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Mathematics, Physics and Biological Engineering, Inner Mongolia University of Science and Technology, Baotou 014010, China. Electronic address: nmcailu@163.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D015496:CD4-Positive T-Lymphocytes; D015894:Genome, Human; D006801:Humans; D009707:Nucleosomes / Q000737:chemistry*; D018911:Trinucleotide Repeats
chemical_list: D009707:Nucleosomes
keywords: Chromatin structures; Friedreich's ataxia; Trinucleotide repeats