Systematic identification of transcriptional regulatory modules from protein-protein interaction networks.
Systematic identification of transcriptional regulatory modules from protein-protein interaction networks.
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DOI：
10.1093/nar/gkt913
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发表时间：
2014-01
影响因子：
14.9
通讯作者：
Miranda-Saavedra D
中科院分区：
文献类型：
--
作者：
Diez D;Hutchins AP;Miranda-Saavedra D
转录因子(TF)与辅因子结合形成转录调控模块(TRMS)，具有时空特异性调节基因表达的功能。在这里，我们提出了一种新的通用方法(RTRM)来重建TRMS，它整合了来自TF结合、细胞类型特异性基因表达和蛋白质-蛋白质相互作用的基因组信息。应用rTRM重建胚胎干细胞(ESC)和造血干细胞(HSC)、神经前体细胞、滋养层干细胞和不同类型终末分化的CD4+T细胞的TRMS。ESC和HSC TRM的预测非常精确，产生了77和96个蛋白质，其中75%的∼已被证明独立地参与了这些细胞类型的调节。此外，rTRM成功地发现了大量在ESCs和HSCs中具有已知作用的桥联蛋白，由于它们缺乏结合特定DNA序列的能力，因此无法仅用基因组方法进行鉴定。这突显了rTRM相对于忽略PPI信息的其他方法的优势，因为蛋白质需要与其他蛋白质相互作用形成复合体并执行特定功能。对赋予主控调控因子选择特定基因组位置、调节局部表观遗传学特征和整合多种信号的辅助因子的预测和实验验证，不仅将为这些因子的运作方式提供重要的机制见解，还将为导致疾病的异常转录状态提供重要的机制见解。
Transcription factors (TFs) combine with co-factors to form transcriptional regulatory modules (TRMs) that regulate gene expression programs with spatiotemporal specificity. Here we present a novel and generic method (rTRM) for the reconstruction of TRMs that integrates genomic information from TF binding, cell type-specific gene expression and protein–protein interactions. rTRM was applied to reconstruct the TRMs specific for embryonic stem cells (ESC) and hematopoietic stem cells (HSC), neural progenitor cells, trophoblast stem cells and distinct types of terminally differentiated CD4+ T cells. The ESC and HSC TRM predictions were highly precise, yielding 77 and 96 proteins, of which ∼75% have been independently shown to be involved in the regulation of these cell types. Furthermore, rTRM successfully identified a large number of bridging proteins with known roles in ESCs and HSCs, which could not have been identified using genomic approaches alone, as they lack the ability to bind specific DNA sequences. This highlights the advantage of rTRM over other methods that ignore PPI information, as proteins need to interact with other proteins to form complexes and perform specific functions. The prediction and experimental validation of the co-factors that endow master regulatory TFs with the capacity to select specific genomic sites, modulate the local epigenetic profile and integrate multiple signals will provide important mechanistic insights not only into how such TFs operate, but also into abnormal transcriptional states leading to disease.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
21.3
作者：
Feng, Bo;Jiang, Jianming;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
4.8
作者：
Kaeser, Matthias D.;Aslanian, Aaron;Emerson, Beverly M.
通讯作者：
Emerson, Beverly M.
影响因子：
5.2
作者：
Khalfallah, Olfa;Rouleau, Matthieu;Lalli, Enzo
通讯作者：
Lalli, Enzo
影响因子：
12.3
作者：
Frietze S;Wang R;Yao L;Tak YG;Ye Z;Gaddis M;Witt H;Farnham PJ;Jin VX
通讯作者：
Jin VX