High-throughput sequencing reveals a simple model of nucleosome energetics
High-throughput sequencing reveals a simple model of nucleosome energetics
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DOI：
10.1073/pnas.1003838107
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发表时间：
2010-12-07
影响因子：
11.1
通讯作者：
Morozov, Alexandre V.
中科院分区：
文献类型：
--
作者：
Locke, George;Tolkunov, Denis;Morozov, Alexandre V.
我们使用全基因组核小体图来研究内在组蛋白- dna相互作用的序列特异性。与以前的方法相比，我们采用了在任意外部电位的有限大小颗粒的经典一维流体和dna结合组蛋白八聚体阵列之间的类比。我们推导了一个解析解，直接从高通量实验中测量的核小体占位率推断核小体形成的自由能。然后，通过将自由能序列的特定部分与分配给单个核苷酸基序的能量总和相匹配来捕获它们。我们已经开发了越来越复杂和空间分辨率的层次模型，建立了核小体占用可以通过核小体和连接体DNA序列之间单核苷酸和二核苷酸含量的系统差异来解释，而周期性的二核苷酸分布和较长的序列基序起着次要作用。此外，类似的序列特征在对照实验中被展示出来，在对照实验中，无核小体的基因组DNA要么被超声处理，要么被微球菌核酸酶消化，这使得目前基于高通量核小体定位图的预测有可能受到实验伪影的影响。
We use genome-wide nucleosome maps to study sequence specificity of intrinsic histone-DNA interactions. In contrast with previous approaches, we employ an analogy between a classical one-dimensional fluid of finite-size particles in an arbitrary external potential and arrays of DNA-bound histone octamers. We derive an analytical solution to infer free energies of nucleosome formation directly from nucleosome occupancies measured in high-throughput experiments. The sequence-specific part of free energies is then captured by fitting them to a sum of energies assigned to individual nucleotide motifs. We have developed hierarchical models of increasing complexity and spatial resolution, establishing that nucleosome occupancies can be explained by systematic differences in mono-and dinucleotide content between nucleosomal and linker DNA sequences, with periodic dinucleotide distributions and longer sequence motifs playing a minor role. Furthermore, similar sequence signatures are exhibited by control experiments in which nucleosome-free genomic DNA is either sonicated or digested with micrococcal nuclease, making it possible that current predictions based on high-throughput nucleosome-positioning maps are biased by experimental artifacts.