Modeling the relative relationship of transcription factor binding and histone modifications to gene expression levels in mouse embryonic stem cells.
Modeling the relative relationship of transcription factor binding and histone modifications to gene expression levels in mouse embryonic stem cells.
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DOI：
10.1093/nar/gkr752
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发表时间：
2012-01
影响因子：
14.9
通讯作者：
Gerstein M
中科院分区：
文献类型：
--
作者：
Cheng C;Gerstein M
转录因子（TF）结合和组蛋白修饰（HM）对于精确控制基因表达是重要的。因此，我们构建了统计模型，将这些与小鼠胚胎干细胞中的基因表达水平联系起来。虽然TF结合和HM都是基因表达水平的高度“预测”，（在统计学上，但可能不是严格的机械意义上），我们发现它们在预测强度的空间模式上显示出明显的差异：TF结合在以基因转录起始位点为中心的小DNA区域中实现了最高的预测能力，而HM在基因周围的广泛区域中表现出高预测能力。有趣的是，我们的研究结果表明，TF结合和HM是冗余的，在严格的统计意义上预测基因表达。我们还表明，我们的TF和HM模型是细胞系特异性的;具体而言，TF结合和HM更能预测同一细胞系中的基因表达，并且细胞系之间的差异基因表达可通过差异HM预测。最后，我们发现，仅在蛋白质编码基因上训练的模型可以预测microRNA的表达水平，这表明TF和HM对它们的调控可能与蛋白质编码基因的调控机制相似。
Transcription factor (TF) binding and histone modification (HM) are important for the precise control of gene expression. Hence, we constructed statistical models to relate these to gene expression levels in mouse embryonic stem cells. While both TF binding and HMs are highly ‘predictive’ of gene expression levels (in a statistical, but perhaps not strictly mechanistic, sense), we find they show distinct differences in the spatial patterning of their predictive strength: TF binding achieved the highest predictive power in a small DNA region centered at the transcription start sites of genes, while the HMs exhibited high predictive powers across a wide region around genes. Intriguingly, our results suggest that TF binding and HMs are redundant in strict statistical sense for predicting gene expression. We also show that our TF and HM models are cell line specific; specifically, TF binding and HM are more predictive of gene expression in the same cell line, and the differential gene expression between cell lines is predictable by differential HMs. Finally, we found that the models trained solely on protein-coding genes are predictive of expression levels of microRNAs, suggesting that their regulation by TFs and HMs may share a similar mechanism to that for protein-coding genes.
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影响因子：
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作者：
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通讯作者：
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DOI：
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