Marathe Arvind, Bansal Manju
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 12, India.
BMC Struct Biol. 2011 Jan 5;11:1. doi: 10.1186/1472-6807-11-1.
A nucleosome is the fundamental repeating unit of the eukaryotic chromosome. It has been shown that the positioning of a majority of nucleosomes is primarily controlled by factors other than the intrinsic preference of the DNA sequence. One of the key questions in this context is the role, if any, that can be played by the variability of nucleosomal DNA structure.
In this study, we have addressed this question by analysing the variability at the dinucleotide and trinucleotide as well as longer length scales in a dataset of nucleosome X-ray crystal structures. We observe that the nucleosome structure displays remarkable local level structural versatility within the B-DNA family. The nucleosomal DNA also incorporates a large number of kinks.
Based on our results, we propose that the local and global level versatility of B-DNA structure may be a significant factor modulating the formation of nucleosomes in the vicinity of high-plasticity genes, and in varying the probability of binding by regulatory proteins. Hence, these factors should be incorporated in the prediction algorithms and there may not be a unique 'template' for predicting putative nucleosome sequences. In addition, the multimodal distribution of dinucleotide parameters for some steps and the presence of a large number of kinks in the nucleosomal DNA structure indicate that the linear elastic model, used by several algorithms to predict the energetic cost of nucleosome formation, may lead to incorrect results.
核小体是真核染色体的基本重复单位。研究表明,大多数核小体的定位主要受DNA序列固有偏好以外的因素控制。在这种情况下,一个关键问题是核小体DNA结构的变异性可能发挥的作用(如果有的话)。
在本研究中,我们通过分析核小体X射线晶体结构数据集在二核苷酸、三核苷酸以及更长长度尺度上的变异性来解决这个问题。我们观察到,核小体结构在B-DNA家族中展现出显著的局部结构多样性。核小体DNA还包含大量的弯折。
基于我们的结果,我们提出B-DNA结构在局部和全局水平上的多样性可能是调节高可塑性基因附近核小体形成以及改变调节蛋白结合概率的一个重要因素。因此,这些因素应纳入预测算法中,并且可能不存在预测假定核小体序列的唯一“模板”。此外,某些步的二核苷酸参数的多峰分布以及核小体DNA结构中大量弯折的存在表明,几种用于预测核小体形成能量成本的算法所使用的线性弹性模型可能会导致错误结果。