Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers.
Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers.
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DOI：
10.1101/gr.154922.113
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发表时间：
2013-08
期刊：
影响因子：
7
通讯作者：
Prabhakar S
中科院分区：
文献类型：
--
作者：
Jankowski A;Szczurek E;Jauch R;Tiuryn J;Prabhakar S
转录因子（TF）与基因组调控区中特定基序的结合通常是单独研究的。然而，为了阐明转录调控的机制，它是必不可少的，以确定哪些转录因子结合DNA合作作为二聚体，并推断这些相互作用的确切性质。到目前为止，只有少数这样的二聚体复合物是已知的。在这里，我们提出了一种算法，用于预测细胞类型特异性TF-TF二聚化DNA上的大规模，使用DNase I超敏反应数据从78人细胞系。我们代表了宇宙中可能的TF复合物，其相应的基序复合物，并分析了它们发生在细胞类型特异性DNA酶I超敏位点。基于14亿次基序复合物富集测试，我们预测了603种高度显著的细胞类型特异性TF二聚体，其中绝大多数是新的。我们的预测包括76%（19/25）的已知二聚体复合物，并显示出显着的重叠与蛋白质-蛋白质相互作用的实验数据库。它们也独立地支持进化保守，以及DNA酶I消化模式的定量变化。值得注意的是，已知的和预测的TF二聚体几乎总是高度紧凑和刚性间隔，这表明TF二聚体非常接近它们的伴侣，这导致对DNA结合复合物的结构的严格限制。总的来说，我们的研究结果表明，染色质开放性配置文件是高度预测细胞类型特异性TF-TF相互作用。此外，合作TF二聚化似乎是一种普遍的现象，在大多数细胞类型中预测有多个TF复合物。
The binding of transcription factors (TFs) to their specific motifs in genomic regulatory regions is commonly studied in isolation. However, in order to elucidate the mechanisms of transcriptional regulation, it is essential to determine which TFs bind DNA cooperatively as dimers and to infer the precise nature of these interactions. So far, only a small number of such dimeric complexes are known. Here, we present an algorithm for predicting cell-type–specific TF–TF dimerization on DNA on a large scale, using DNase I hypersensitivity data from 78 human cell lines. We represented the universe of possible TF complexes by their corresponding motif complexes, and analyzed their occurrence at cell-type–specific DNase I hypersensitive sites. Based on ∼1.4 billion tests for motif complex enrichment, we predicted 603 highly significant cell-type–specific TF dimers, the vast majority of which are novel. Our predictions included 76% (19/25) of the known dimeric complexes and showed significant overlap with an experimental database of protein–protein interactions. They were also independently supported by evolutionary conservation, as well as quantitative variation in DNase I digestion patterns. Notably, the known and predicted TF dimers were almost always highly compact and rigidly spaced, suggesting that TFs dimerize in close proximity to their partners, which results in strict constraints on the structure of the DNA-bound complex. Overall, our results indicate that chromatin openness profiles are highly predictive of cell-type–specific TF–TF interactions. Moreover, cooperative TF dimerization seems to be a widespread phenomenon, with multiple TF complexes predicted in most cell types.
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DOI：
10.1073/pnas.231608898
发表时间：
2002-01-22
影响因子：
11.1
作者：
Berman, BP;Nibu, Y;Eisen, MB
通讯作者：
Eisen, MB
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
14.9
作者：
Baburajendran N;Jauch R;Tan CY;Narasimhan K;Kolatkar PR
通讯作者：
Kolatkar PR
影响因子：
64.5
作者：
Lupien, Mathieu;Eeckhoute, Jerome;Brown, Myles
通讯作者：
Brown, Myles
影响因子：
7
作者：
Boyle, Alan P.;Song, Lingyun;Furey, Terrence S.
通讯作者：
Furey, Terrence S.