Genomic sequence is highly predictive of local nucleosome depletion.
Genomic sequence is highly predictive of local nucleosome depletion.
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基因组序列高度预测了局部核小体耗竭。
DOI：
10.1371/journal.pcbi.0040013
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发表时间：
2008-01
影响因子：
4.3
通讯作者：
Liu JS
中科院分区：
文献类型：
--
作者：
Yuan GC;Liu JS
通过核小体定位调节 DNA 可及性对于转录控制非常重要。已经开发出计算模型来根据 DNA 序列预测全基因组核小体位置，但这些模型仅考虑核小体序列，这可能限制了它们的能力。我们开发了一种统计多分辨率方法来识别序列特征（称为 N 分数），该序列特征可区分核小体结合 DNA 和非核小体 DNA。这种新方法显着提高了预测精度。序列信息对局部核小体富集或耗尽具有高度预测性，而精确位置的预测仅比空模型稍微准确，这表明其他调节因素在微调核小体位置中的重要性。启动子区域的 N 分数与基因表达水平负相关。调节元件在低 N 值区域富集。虽然我们的模型源自酵母数据，但根据该模型计算出的 N 分数模式与最新的人类高分辨率蛋白质结合数据非常吻合。真核基因组被包装到染色质中。染色质不仅使相对较长的基因组能够装入微小的细胞核中，而且还发挥着重要的调节作用。核小体是染色质的基本重复单位。高分辨率平铺阵列实验表明，许多核小体在体内定位良好，与重要的调节作用一致。然而，决定核小体定位的机制仍然知之甚少。我们开发了一种新的计算方法，仅使用基因组序列信息来预测核小体位置。该方法检测区分核小体序列和接头序列的周期性序列特征。我们表明，与之前的研究相比，这种方法显着提高了预测能力。有趣的是，最可预测的区域往往位于需要严格监管的地方，即转录起始位点附近。该模型预测核小体占据不是由短 DNA 序列基序强烈控制，而是由短元素规则组织成周期性模式逐步控制。我们还提供了证据表明核小体结合的序列特异性从酵母到人类都是保守的。
The regulation of DNA accessibility through nucleosome positioning is important for transcription control. Computational models have been developed to predict genome-wide nucleosome positions from DNA sequences, but these models consider only nucleosome sequences, which may have limited their power. We developed a statistical multi-resolution approach to identify a sequence signature, called the N-score, that distinguishes nucleosome binding DNA from non-nucleosome DNA. This new approach has significantly improved the prediction accuracy. The sequence information is highly predictive for local nucleosome enrichment or depletion, whereas predictions of the exact positions are only modestly more accurate than a null model, suggesting the importance of other regulatory factors in fine-tuning the nucleosome positions. The N-score in promoter regions is negatively correlated with gene expression levels. Regulatory elements are enriched in low N-score regions. While our model is derived from yeast data, the N-score pattern computed from this model agrees well with recent high-resolution protein-binding data in human. A eukaryotic genome is packaged into chromatin. The chromatin not only makes it possible to fit the relatively long genome into a tiny nucleus, but also plays an important regulatory role. The nucleosome is the fundamental repeating unit of chromatin. High-resolution tiling array experiments have shown that many nucleosomes are well-positioned in vivo, consistent with an important regulatory role. However, the mechanisms that determine nucleosome positioning are still poorly understood. We have developed a novel computational method for predicting nucleosome positions using only the genomic sequence information. The method detects periodic sequence signatures that discriminate nucleosome sequences from linker sequences. We show that this approach has significantly improved predictive power compared to previous studies. Interestingly, the most predictable regions tend to be located where stringent regulations are needed, i.e., the neighborhood of a transcription start site. This model predicts that nucleosome occupancy is not strongly controlled by short DNA sequence motifs but rather progressively controlled by regular organization of short elements into periodic patterns. We also provide evidence that sequence specificity for nucleosome binding is conserved from yeast to human.
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影响因子：
30.8
作者：
Ioshikhes, Ilya P.;Albert, Istvan;Pugh, B. Franklin
通讯作者：
Pugh, B. Franklin
DOI：
10.1073/pnas.94.4.1183
发表时间：
1997-02-18
影响因子：
11.1
作者：
Lowary, PT;Widom, J
通讯作者：
Widom, J
影响因子：
64.5
作者：
Kim, Tae Hoon;Abdullaev, Ziedulla K.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.5
作者：
Basehoar, AD;Zanton, SJ;Pugh, BF
通讯作者：
Pugh, BF
影响因子：
56.9
作者：
Dion, Michael F.;Kaplan, Tommy;Rando, Oliver J.
通讯作者：
Rando, Oliver J.