Nucleosome positioning signals in genomic DNA
Nucleosome positioning signals in genomic DNA
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DOI：
10.1101/gr.6101007
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发表时间：
2007-08-01
期刊：
影响因子：
7
通讯作者：
Weng, Zhiping
中科院分区：
文献类型：
--
作者：
Peckham, Heather E.;Thurman, Robert E.;Weng, Zhiping
尽管组蛋白几乎可以在任何基因组序列上形成核小体，但 DNA 序列在其结合亲和力方面表现出相当大的变异性。我们使用了酿酒酵母的 DNA 序列，其核小体结合亲和力已通过实验确定（Yuan 等人，2005）来训练支持向量机来识别任何给定 DNA 序列的核小体形成潜力。核小体形成潜力最准确预测的 DNA 序列是那些含有强核小体形成或抑制信号的 DNA 序列，并且在具有连续核小体形成或抑制信号的基因组 DNA 的核小体长度范围内发现。我们准确地预测了通过实验确定的酿酒酵母启动子区域的核小体位置，并在最近研究的 199 个中心对齐单核小体中识别出强周期性（Segal 等，2006），尽管没有用于训练支持向量机的周期性信息。我们的分析表明，只有一部分核小体可能由内在序列信号定位。这一观察结果与现有的实验数据一致，并且与核小体定位代码的提议不一致。最后，我们表明，在酿酒酵母中，内在核小体定位信号在启动子区域比在开放阅读框中更具抑制性和更多可变性。
Although histones can form nucleosomes on virtually any genomic sequence, DNA sequences show considerable variability in their binding affinity. We have used DNA sequences of Saccharomyces cerevisiae whose nucleosome binding affinities have been experimentally determined (Yuan et al. 2005) to train a support vector machine to identify the nucleosome formation potential of any given sequence of DNA. The DNA sequences whose nucleosome formation potential are most accurately predicted are those that contain strong nucleosome forming or inhibiting signals and are found within nucleosome length stretches of genomic DNA with continuous nucleosome formation or inhibition signals. We have accurately predicted the experimentally determined nucleosome positions across a well-characterized promoter region of S. cerevisiae and identified strong periodicity within 199 center-aligned mononucleosomes studied recently (Segal et al. 2006) despite there being no periodicity information used to train the support vector machine. Our analysis suggests that only a subset of nucleosomes are likely to be positioned by intrinsic sequence signals. This observation is consistent with the available experimental data and is inconsistent with the proposal of a nucleosome positioning code. Finally, we show that intrinsic nucleosome positioning signals are both more inhibitory and more variable in promoter regions than in open reading frames in S. cerevisiae.