Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.
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DOI:
10.15252/msb.20145504
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发表时间:
2015-01-21
影响因子:
9.9
通讯作者:
Chen J
Chen J
中科院分区:
生物学1区
文献类型:
--
作者:
Li X;Wang W;Wang J;Malovannaya A;Xi Y;Li W;Guerra R;Hawke DH;Qin J;Chen J

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转录因子是细胞信号传导途径的最终靶点和执行者,目前对转录因子如何受蛋白质-蛋白质相互作用调控的认识仍然有限。在这里,我们进行了可溶性和染色质相关的复合物的56 TF,包括参与发展和癌症的许多信号通路的目标,和37个成员的叉头盒(FOX)TF家族的蛋白质组学分析。使用串联亲和纯化和质谱(TAP/MS),我们进行了214次纯化,并鉴定了2,156种高置信度的蛋白质-蛋白质相互作用。我们发现大多数TF在染色质上和染色质外形成非常不同的蛋白质复合物。使用这个数据集,我们对一般或特定TF的转录相关或不相关调节因子进行了分类。我们的研究为大量TF提供了蛋白质-蛋白质相互作用网络的宝贵资源,并强调了TF形成不同位置特异性蛋白质复合物的一般原则,这些蛋白质复合物与这些TF的不同调节和不同功能相关。
The current knowledge on how transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated by protein–protein interactions remains limited. Here, we performed proteomics analyses of soluble and chromatin-associated complexes of 56 TFs, including the targets of many signalling pathways involved in development and cancer, and 37 members of the Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high-confident protein–protein interactions. We found that most TFs form very distinct protein complexes on and off chromatin. Using this data set, we categorized the transcription-related or unrelated regulators for general or specific TFs. Our study offers a valuable resource of protein–protein interaction networks for a large number of TFs and underscores the general principle that TFs form distinct location-specific protein complexes that are associated with the different regulation and diverse functions of these TFs.