Quantitative Test of the Barrier Nucleosome Model for Statistical Positioning of Nucleosomes Up- and Downstream of Transcription Start Sites
Quantitative Test of the Barrier Nucleosome Model for Statistical Positioning of Nucleosomes Up- and Downstream of Transcription Start Sites
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DOI：
10.1371/journal.pcbi.1000891
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发表时间：
2010-08-01
影响因子：
4.3
通讯作者：
Gerland, Ulrich
中科院分区：
文献类型：
--
作者：
Moebius, Wolfram;Gerland, Ulrich
核小体在真核生物基因组中的位置决定了DNA序列的哪些部分容易被调控蛋白访问，哪些不能。全基因组核小体位置图显示了转录起始点周围的显著模式，涉及核小体无性区(NFR)，两侧是平均核小体密度的明显周期性模式。虽然周期模式清楚地反映了定位良好的核小体，但定位机制不太清楚。Mavrich等人最近的一项实验研究。他认为，在酿酒酵母中观察到的模式定性地与“屏障核小体模型”一致，在该模型中，振荡模式是由Kornberg和Stryer的统计定位机制创建的。另一方面，有明确的证据表明核小体的内在序列偏好，目前还不清楚这些序列偏好在多大程度上影响观察到的模式。为了验证屏障核小体模型，我们对NFR上游和下游的酵母核小体定位数据进行了定量分析。我们的分析是基于统计物理的Tonks模型，该模型量化了核小体的排除体积相互作用和它们的位置熵之间的相互作用。我们发现，尽管NFR两侧的典型模式不同，但它们都是由相同的物理模型、相同的参数、但不同的边界条件来定量描述的。推测的边界条件表明，NFR下游的第一个核小体(+1核小体)通常是直接定位的，而上游的第一个核小体在统计学上是通过核小体排斥DNA区域定位的。这些边界条件可以被局部编码到基因组序列中，显著地塑造了核小体在高达1,000个碱基对的范围内的统计分布。
The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which are not. Genome-wide maps of nucleosome positions have revealed a salient pattern around transcription start sites, involving a nucleosome-free region (NFR) flanked by a pronounced periodic pattern in the average nucleosome density. While the periodic pattern clearly reflects well-positioned nucleosomes, the positioning mechanism is less clear. A recent experimental study by Mavrich et al. argued that the pattern observed in Saccharomyces cerevisiae is qualitatively consistent with a "barrier nucleosome model," in which the oscillatory pattern is created by the statistical positioning mechanism of Kornberg and Stryer. On the other hand, there is clear evidence for intrinsic sequence preferences of nucleosomes, and it is unclear to what extent these sequence preferences affect the observed pattern. To test the barrier nucleosome model, we quantitatively analyze yeast nucleosome positioning data both up- and downstream from NFRs. Our analysis is based on the Tonks model of statistical physics which quantifies the interplay between the excluded-volume interaction of nucleosomes and their positional entropy. We find that although the typical patterns on the two sides of the NFR are different, they are both quantitatively described by the same physical model with the same parameters, but different boundary conditions. The inferred boundary conditions suggest that the first nucleosome downstream from the NFR (the +1 nucleosome) is typically directly positioned while the first nucleosome upstream is statistically positioned via a nucleosome-repelling DNA region. These boundary conditions, which can be locally encoded into the genome sequence, significantly shape the statistical distribution of nucleosomes over a range of up to,1,000 bp to each side.