Predicting promoter activities of primary human DNA sequences.

Predicting promoter activities of primary human DNA sequences.
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DOI:
10.1093/nar/gkr173
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发表时间:
2011-06
影响因子:
14.9
通讯作者:
Suzuki Y
Suzuki Y
中科院分区:
生物学2区
文献类型:
--
作者:
Irie T;Park SJ;Yamashita R;Seki M;Yada T;Sugano S;Nakai K;Suzuki Y

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我们开发了一个计算机程序,可以预测原始人类DNA序列的内在启动子活性。我们使用定量荧光素酶测定观察启动子活性,并使用多元线性回归产生预测模型。我们的程序实现了预测准确度之间的相关系数为0.87的预测和观察到的启动子活动。我们评估了预测的准确性程序使用大量的测序分析在体内的转录起始位点。我们发现,它仍然是难以预测的转录水平在体内以严格的定量方式,但是,它是可能的,以选择在一个给定的细胞中的其他沉默的启动子的活性启动子。使用这个程序,我们分析了整个人类基因组的转录景观。我们证明,许多人类基因组区域具有潜在的启动子活性,一些以前未表征的puppet非蛋白编码转录本的表达可以通过我们的预测模型来解释。此外,我们发现,核小体偶尔形成开放的染色质结构与RNA聚合酶II招聘的程序预测显着的启动子活性,虽然没有观察到转录本。
We developed a computer program that can predict the intrinsic promoter activities of primary human DNA sequences. We observed promoter activity using a quantitative luciferase assay and generated a prediction model using multiple linear regression. Our program achieved a prediction accuracy correlation coefficient of 0.87 between the predicted and observed promoter activities. We evaluated the prediction accuracy of the program using massive sequencing analysis of transcriptional start sites in vivo. We found that it is still difficult to predict transcript levels in a strictly quantitative manner in vivo; however, it was possible to select active promoters in a given cell from the other silent promoters. Using this program, we analyzed the transcriptional landscape of the entire human genome. We demonstrate that many human genomic regions have potential promoter activity, and the expression of some previously uncharacterized putatively non-protein-coding transcripts can be explained by our prediction model. Furthermore, we found that nucleosomes occasionally formed open chromatin structures with RNA polymerase II recruitment where the program predicted significant promoter activities, although no transcripts were observed.
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