Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.
Nat Struct Mol Biol. 2011 Apr;18(4):510-5. doi: 10.1038/nsmb.2012. Epub 2011 Mar 13.
DNA sequence variations in individual genomes give rise to different phenotypes within the same species. One mechanism in this process is the alteration of chromatin structure due to sequence variation that influences gene regulation. We composed a high-confidence collection of human single-nucleotide polymorphisms and indels based on analysis of publicly available sequencing data and investigated whether the DNA loci associated with stable nucleosome positions are protected against mutations. We addressed how the sequence variation reflects the occupancy profiles of nucleosomes bearing different epigenetic modifications on genome scale. We found that indels are depleted around nucleosome positions of all considered types, whereas single-nucleotide polymorphisms are enriched around the positions of bulk nucleosomes but depleted around the positions of epigenetically modified nucleosomes. These findings indicate an increased level of conservation for the sequences associated with epigenetically modified nucleosomes, highlighting complex organization of the human chromatin.
个体基因组中的 DNA 序列变异导致同一物种内出现不同的表型。在这个过程中，一种机制是由于序列变异导致染色质结构发生改变，从而影响基因调控。我们基于对公开可用测序数据的分析，构建了一个高度可信的人类单核苷酸多态性和插入缺失的集合，并研究了与稳定核小体位置相关的 DNA 位点是否免受突变的影响。我们研究了序列变异如何反映在基因组范围内具有不同表观遗传修饰的核小体的占有率图谱。我们发现，插入缺失在所有考虑类型的核小体位置周围都减少了，而单核苷酸多态性在大量核小体位置周围富集，但在表观遗传修饰核小体位置周围减少。这些发现表明，与表观遗传修饰核小体相关的序列具有更高的保守水平，突出了人类染色质的复杂组织。
