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GAA triplet-repeats cause nucleosome depletion in the human genome

机译：GAA三重重复导致人类基因组中的核小体耗竭

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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.
机译：尽管已经对三核苷酸重复如何影响核小体形成和局部染色质结构进行了许多研究，但是在人类基因组中GAA三联体重复在核小体中的位置仍然难以捉摸。在这项工作中，统计了整个人类基因组中GAA三联体重复周围核小体的占有率。结果表明，在激活和静止的CD4（+）T细胞中，GM三联体重复附近有一个核小体耗尽的区域。此外，A区域经常与GM三联体重复序列的上游区域相邻，并且可以增强GAA三联体重复序列周围的消耗。用含GM的质粒进行的体外染色质重建分析还表明，插入的GAA三重体重复序列使重组质粒组装核小体的能力不稳定。我们的结果表明，GM三联体重复序列对组蛋白的亲和力较低，并且可以改变局部核小体的定位。这些发现可能有助于理解弗里德里希共济失调的机制，共济失调与染色质水平的GM三联体重复有关。 （C）2015 Elsevier Inc保留所有权利。

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