Sequence-dependent nucleosome formation in trinucleotide repeats evaluated by in vivo chemical mapping
Sequence-dependent nucleosome formation in trinucleotide repeats evaluated by in vivo chemical mapping
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通过体内化学作图评估三核苷酸重复中序列依赖性核小体的形成
DOI：
10.1016/j.bbrc.2021.03.155
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Mitsuhiro Shimizu
中科院分区：
文献类型：
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作者：
Koji Katsumata;Yuichi Ichikawa;Tomohiro Fuse;Hitoshi Kurumizaka;Akio Yanagida ;Takeshi Urano;Hiroaki Kato;Mitsuhiro Shimizu
三核苷酸重复序列（Trinucleotide repeat sequences，TRSs）是微卫星的一种，由10类独特的DNA重复序列组成，在许多真核生物基因组中大量存在。TRS的长度是可变的，并且几个TRS的扩展与遗传性神经系统疾病有关。然而，TRS在基因组中的偏态分布和动态特性的根本原因仍然难以捉摸。在这里，我们研究了TRS对核小体形成的影响，在体内组蛋白H4-S47 C定点化学裂解，使用定义明确的酵母微型染色体，其中10个TRS类中的每一个都位于一个定位的核小体的中心区域。结果表明，（AAT）12和（ACT）12在体内是强核小体促进序列，而（AGG）12和（CCG）12在体内是强核小体排斥序列。局部组蛋白结合亲和力分数支持这样的想法，即除了（AGG）12之外，TRS中的核小体形成主要由组蛋白八聚体的亲和力决定。总的来说，我们的研究提出了一个框架，了解TRS的核小体形成能力。
Trinucleotide repeat sequences (TRSs), consisting of 10 unique classes of repeats in DNA, are members of microsatellites and abundantly and non-randomly distributed in many eukaryotic genomes. The lengths of TRSs are mutable, and the expansions of several TRSs are implicated in hereditary neurological diseases. However, the underlying causes of the biased distribution and the dynamic properties of TRSs in the genome remain elusive. Here, we examined the effects of TRSs on nucleosome formationin vivoby histone H4–S47C site-directed chemical cleavages, using well-defined yeast minichromosomes in which each of the ten TRS classes resided in the central region of a positioned nucleosome. We showed that (AAT)12and (ACT)12act as strong nucleosome-promoting sequences, while (AGG)12and (CCG)12act as nucleosome-excluding sequencesin vivo. The local histone binding affinity scores support the idea that nucleosome formation in TRSs, except for (AGG)12, is mainly determined by the affinity for the histone octamers. Overall, our study presents a framework for understanding the nucleosome-forming abilities of TRSs.