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Relating periodicity of nucleosome organization and gene regulation

机译:核小体组织与基因调控的周期性

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Motivation: The relationship between nucleosome positioning and gene regulation is fundamental yet complex. Previous studies on genomic nucleosome positions have revealed a correlation between nucleosome occupancy on promoters and gene expression levels. Many of these studies focused on individual nucleosomes, especially those proximal to transcription start sites. To study the collective effect of multiple nucleosomes on the gene expression, we developed a mathematical approach based on autocorrelation to relate genomic nucleosome organization to gene regulation.Results: We found that nucleosome organization in gene promoters can be well described by autocorrelation transformation. Some promoters show obvious periods in their nucleosome organization, while others have no clear periodicity. The genes with periodic nucleosome organization in promoters tend to be lower expressed than the genes without periodic nucleosome organization. These suggest that regular organization of nucleosomes plays a critical role in gene regulation. To quantitatively associate nucleosome organization and gene expression, we predicted gene expression solely based on nucleosome status and found that nucleosome status accounts for similar to 25% of the observed gene expression variability. Furthermore, we explored the underlying forces that maintain the periodicity in nucleosome organization, namely intrinsic (i.e. DNA sequence) and extrinsic forces (i.e. chromatin remodeling factors). We found that the extrinsic factors play a critical role in maintaining the periodic nucleosome organization.
机译:动机:核小体定位和基因调控之间的关系是基本而复杂的。先前对基因组核小体位置的研究表明,核小体在启动子上的占有与基因表达水平之间存在相关性。这些研究中有许多集中在单个核小体上,尤其是靠近转录起始位点的那些。为了研究多个核小体对基因表达的集体影响,我们开发了一种基于自相关的数学方法,将基因组核小体的组织与基因调控相关。结果:我们发现基因启动子中的核小体的组织可以通过自相关转化很好地描述。一些启动子在其核小体组织中显示明显的时期,而其他启动子则没有明确的周期性。在启动子中具有周期性核小体组织的基因的表达往往比没有周期性核小体组织的基因低。这些表明核小体的规则组织在基因调节中起关键作用。为了定量关联核小体的组织和基因表达,我们仅根据核小体状态预测基因表达,发现核小体状态占观察到的基因表达变异性的25%左右。此外,我们探索了维持核小体组织周期性的潜在力,即内在力(即DNA序列)和​​外在力(即染色质重塑因子)。我们发现,外在因素在维持周期性核小体组织中起关键作用。

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