School of Information Science and Technology, Sun Yat-Sen University, Guangzhou, PR China.
BMC Genomics. 2010 Jan 15;11:33. doi: 10.1186/1471-2164-11-33.
Recently, a number of high-resolution genome-wide maps of nucleosome locations in S. cerevisiae have been derived experimentally. However, nucleosome positions are determined in vivo by the combined effects of numerous factors. Consequently, nucleosomes are not simple static units, which may explain the discrepancies in reported nucleosome positions as measured by different experiments. In order to more accurately depict the genome-wide nucleosome distribution, we integrated multiple nucleosomal positioning datasets using a multi-angle analysis strategy.
To evaluate the contribution of chromatin structure to transcription, we used the vast amount of available nucleosome analyzed data. Analysis of this data allowed for the comprehensive identification of the connections between promoter nucleosome positioning patterns and various transcription-dependent properties. Further, we characterised the function of nucleosome destabilisation in the context of transcription regulation. Our results indicate that genes with similar nucleosome occupancy patterns share general transcription attributes. We identified the local regulatory correlation (LRC) regions for two distinct types of nucleosomes and we assessed their regulatory properties. We also estimated the nucleosome reproducibility and measurement accuracy for high-confidence transcripts. We found that by maintaining a distance of approximately 13 bp between the upstream border of the +1 nucleosome and the transcription start sites (TSSs), the stable +1 nucleosome may form a barrier against the accessibility of the TSS and shape an optimum chromatin conformation for gene regulation. An in-depth analysis of nucleosome positioning in normally growing and heat shock cells suggested that the extent and patterns of nucleosome sliding are associated with gene activation.
Our results, which combine different types of data, suggest that cross-platform information, including discrepancy and consistency, reflects the mechanisms of nucleosome packaging in vivo more faithfully than individual studies. Furthermore, nucleosomes can be divided into two classes according to their stable and dynamic characteristics. We found that two different nucleosome-positioning characteristics may significantly impact transcription programs. Besides, some positioned-nucleosomes are involved in the transition from stable state to dynamic state in response to abrupt environmental changes.
最近,已经从实验中获得了许多酿酒酵母核小体位置的高分辨率全基因组图谱。然而,核小体的位置是由许多因素的综合作用决定的。因此,核小体不是简单的静态单元,这可能解释了不同实验测量的核小体位置报告之间的差异。为了更准确地描绘全基因组核小体分布,我们使用多角度分析策略整合了多个核小体定位数据集。
为了评估染色质结构对转录的贡献,我们使用了大量可分析的核小体数据。对这些数据的分析允许全面识别启动子核小体定位模式与各种转录相关特性之间的联系。此外,我们研究了核小体失稳在转录调控中的作用。我们的研究结果表明,具有相似核小体占有率模式的基因具有一般的转录属性。我们确定了两种不同类型核小体的局部调控相关(LRC)区域,并评估了它们的调控属性。我们还估计了高可信度转录物的核小体重现性和测量精度。我们发现,通过保持+1 核小体上游边界与转录起始位点(TSS)之间约 13bp 的距离,稳定的+1 核小体可能形成 TSS 可及性的屏障,并为基因调控形成最佳的染色质构象。对正常生长和热休克细胞中核小体定位的深入分析表明,核小体滑动的程度和模式与基因激活有关。
我们的研究结果结合了不同类型的数据,表明跨平台信息,包括差异和一致性,比单个研究更真实地反映了体内核小体包装的机制。此外,根据其稳定和动态特性,核小体可以分为两类。我们发现两种不同的核小体定位特征可能对转录程序产生显著影响。此外,一些定位核小体在响应突然的环境变化时,会从稳定状态转变为动态状态。