Bioinformatics and Genomics Group, Centre for Genomic Regulation (CRG), Biomedical Research Park of Barcelona (PRBB), Barcelona, 08003, Catalunya, Spain.
Epigenetics Chromatin. 2010 Nov 12;3(1):20. doi: 10.1186/1756-8935-3-20.
Recent advances in the field of high-throughput genomics have rendered possible the performance of genome-scale studies to define the nucleosomal landscapes of eukaryote genomes. Such analyses are aimed towards providing a better understanding of the process of nucleosome positioning, for which several models have been suggested. Nevertheless, questions regarding the sequence constraints of nucleosomal DNA and how they may have been shaped through evolution remain open. In this paper, we analyze in detail different experimental nucleosome datasets with the aim of providing a hypothesis for the emergence of nucleosome-forming sequences.
We compared the complete sets of nucleosome positions for the budding yeast (Saccharomyces cerevisiae) as defined in the output of two independent experiments with the use of two different experimental techniques. We found that < 10% of the experimentally defined nucleosome positions were consistently positioned in both datasets. This subset of well-positioned nucleosomes, when compared with the bulk, was shown to have particular properties at both sequence and structural levels. Consistently positioned nucleosomes were also shown to occur preferentially in pairs of dinucleosomes, and to be surprisingly less conserved compared with their adjacent nucleosome-free linkers.
Our findings may be combined into a hypothesis for the emergence of a weak nucleosome-positioning code. According to this hypothesis, consistent nucleosomes may be partly guided by nearby nucleosome-free regions through statistical positioning. Once established, a set of well-positioned consistent nucleosomes may impose secondary constraints that further shape the structure of the underlying DNA. We were able to capture these constraints through the application of a recently introduced structural property that is related to the symmetry of DNA curvature. Furthermore, we found that both consistently positioned nucleosomes and their adjacent nucleosome-free regions show an increased tendency towards conservation of this structural feature.
高通量基因组学领域的最新进展使得对真核基因组核小体景观进行全基因组规模研究成为可能。这些分析旨在更好地了解核小体定位的过程,为此已经提出了几种模型。然而,关于核小体 DNA 的序列限制以及它们如何通过进化形成的问题仍然存在。在本文中,我们详细分析了不同的实验核小体数据集,旨在为核小体形成序列的出现提供一个假设。
我们使用两种不同的实验技术,比较了两个独立实验输出的酿酒酵母(Saccharomyces cerevisiae)完整核小体位置数据集。我们发现,在两个数据集中有 <10%的实验定义的核小体位置是一致的。与大部分核小体相比,这组定位良好的核小体在序列和结构水平上都具有特殊的性质。一致定位的核小体也优先出现在双核小体对中,并且与它们相邻的无核小体连接相比,出乎意料地不那么保守。
我们的发现可以结合起来,形成一个关于弱核小体定位密码出现的假设。根据这个假设,一致定位的核小体可能部分通过统计定位来指导附近无核小体区域。一旦建立起来,一组定位良好的一致核小体可能会施加进一步塑造潜在 DNA 结构的二级约束。我们能够通过应用最近引入的与 DNA 曲率对称性相关的结构特性来捕获这些约束。此外,我们发现一致定位的核小体及其相邻的无核小体区域都表现出这种结构特征的增加保守性。