Impact of chromatin structure on sequence variability in the human genome.
Impact of chromatin structure on sequence variability in the human genome.
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DOI：
10.1038/nsmb.2012
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发表时间：
2011-04
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
同一物种内个体基因组中的DNA序列变异引起不同的表型。该过程中的一种机制是由于影响下游基因调控的序列变异导致的染色质结构的改变。在这项研究中，我们组成了一个高置信度的收集人类indel和SNP的基础上，分析了一个大的公开可用的测序数据集，并调查是否与稳定的核小体位置相关的DNA位点的序列突变的保护。我们解决如何反映在不同类型的核小体在调控序列和全基因组的占有率的序列变异。我们发现，插入缺失耗尽周围的所有考虑类型的核小体的位置; SNPs，另一方面，丰富的散装核小体的位置周围，但耗尽周围的位置优先被表观遗传修饰的核小体。这种行为表明与表观遗传修饰的核小体相关的序列的保守性水平增加，并突出了人染色质的复杂组织。
DNA sequence variations in individual genomes within the same species give rise to different phenotypes. One mechanism in this process is alteration of chromatin structure due to sequence variation that impacts gene regulation downstream. In this study, we compose a high-confidence collection of human indels and SNPs based on the analysis of a large set of publicly available sequencing data and investigate whether the DNA loci associated with stable nucleosome positions are protected against sequence mutations. We address how the sequence variation is reflected in the occupancy profiles of nucleosomes of different types at regulatory sequences and genome-wide. We find that indels are depleted around nucleosome positions of all considered types; SNPs, on the other hand, are enriched around the positions of bulk nucleosomes but depleted around the positions preferentially occupied by epigenetically modified nucleosomes. Such a behavior indicates an increased level of conservation for the sequences associated with epigenetically modified nucleosomes and highlights complex organization of the human chromatin.
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