Modeling co-occupancy of transcription factors using chromatin features.
Modeling co-occupancy of transcription factors using chromatin features.
复制标题
使用染色质特征对转录因子的共存进行建模。
DOI：
10.1093/nar/gkv1281
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发表时间：
2016-03-18
影响因子：
14.9
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Liu L;Zhao W;Zhou X
基因表达的调节需要转录因子（TF）和表观遗传修饰，并且已经发现了这两种类型的因子之间的相互作用。然而，染色质特征和TF-TF共占有率之间的关系的研究仍然有限。在这里，我们揭示的关系，首先说明不同的配置文件模式的染色质特征相关的不同的结合事件，包括单一的TF结合和TF-TF共占用71 TF从5个人类细胞系。我们进一步实施了统计分析，通过使用染色质特征（包括DNA酶I超敏反应、11种组蛋白修饰（HM）和GC含量）准确预测基因组范围内的共占据来证明这种关系。值得注意的是，我们的研究结果表明，染色质特征的组合可以在五个细胞中进行准确的预测。对于单个染色质特征，DNase I能够实现高度一致的预测。H3 K27 ac、H3 K4 me 2、H3 K4 me 3和H3 K9 ac是比其它HM更可靠的预测因子。尽管11种HM的组合实现了准确的预测，但当从一种细胞获得的模型应用于其他细胞时，它们的预测能力变化很大，表明HM和TF-TF共占有之间的关系是细胞类型依赖性的。GC含量不是一个可靠的预测因子，但是将GC含量添加到任何其他特征中可以增强其预测能力。总之，我们的结果阐明了TF-TF共占有率和染色质特征之间的密切关系。
Regulation of gene expression requires both transcription factor (TFs) and epigenetic modifications, and interplays between the two types of factors have been discovered. However study of relationships between chromatin features and TF–TF co-occupancy remains limited. Here, we revealed the relationship by first illustrating distinct profile patterns of chromatin features related to different binding events, including single TF binding and TF–TF co-occupancy of 71 TFs from five human cell lines. We further implemented statistical analyses to demonstrate the relationship by accurately predicting co-occupancy genome-widely using chromatin features including DNase I hypersensitivity, 11 histone modifications (HMs) and GC content. Remarkably, our results showed that the combination of chromatin features enables accurate predictions across the five cells. For individual chromatin features, DNase I enables high and consistent predictions. H3K27ac, H3K4me 2, H3K4me3 and H3K9ac are more reliable predictors than other HMs. Although the combination of 11 HMs achieves accurate predictions, their predictive ability varies considerably when a model obtained from one cell is applied to others, indicating relationship between HMs and TF–TF co-occupancy is cell type dependent. GC content is not a reliable predictor, but the addition of GC content to any other features enhances their predictive ability. Together, our results elucidate a strong relationship between TF–TF co-occupancy and chromatin features.