Dissecting nucleosome free regions by a segmental semi-Markov model.

Dissecting nucleosome free regions by a segmental semi-Markov model.
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DOI:
10.1371/journal.pone.0004721
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Li KC
Li KC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sun W;Xie W;Xu F;Grunstein M;Li KC

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核小体自由区在包括基因调控在内的多种生物学过程中发挥着重要作用。每个单独的NFR的全基因组定量画像,其起始和结束位置,长度和核小体消耗程度对于揭示基因调控和染色质组织的异质性至关重要。通过平均核小体占用水平,先前的研究已经确定了许多基因的启动子区域中存在NFR。然而,评价单个NFR的定量特征需要NFR调用方法。在这项研究中,我们提出了一种统计方法来确定模式的核小体占用的全基因组测量的NFR。该方法是基于一个适当设计的分段半马尔可夫模型,它可以捕捉每一个NFR模式,并输出其定量特征。我们的研究结果表明,大多数NFR位于基因间区或启动子,长度约为400- 600 bp,并有不同程度的核小体缺失。我们的定量NFR映射允许从NFR驱逐组蛋白的转录机制和DNA序列的相对影响的调查。我们发现,虽然这两个因素有显着的整体效果,其具体的贡献不同亚型的NFR。我们的方法强调的变化,而不是核小体自由区域的共识,为探索染色质生物学的许多微妙的动态方面奠定了基调。
Nucleosome free regions (NFRs) play important roles in diverse biological processes including gene regulation. A genome-wide quantitative portrait of each individual NFR, with their starting and ending positions, lengths, and degrees of nucleosome depletion is critical for revealing the heterogeneity of gene regulation and chromatin organization. By averaging nucleosome occupancy levels, previous studies have identified the presence of NFRs in the promoter regions across many genes. However, evaluation of the quantitative characteristics of individual NFRs requires an NFR calling method. In this study, we propose a statistical method to identify the patterns of NFRs from a genome-wide measurement of nucleosome occupancy. This method is based on an appropriately designed segmental semi-Markov model, which can capture each NFR pattern and output its quantitative characterizations. Our results show that the majority of the NFRs are located in intergenic regions or promoters with a length of about 400–600bp and varying degrees of nucleosome depletion. Our quantitative NFR mapping allows for an investigation of the relative impacts of transcription machinery and DNA sequence in evicting histones from NFRs. We show that while both factors have significant overall effects, their specific contributions vary across different subtypes of NFRs. The emphasis of our approach on the variation rather than the consensus of nucleosome free regions sets the tone for enabling the exploration of many subtler dynamic aspects of chromatin biology.
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