Transcriptional regulation of protein complexes within and across species
Transcriptional regulation of protein complexes within and across species
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DOI：
10.1073/pnas.0606914104
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发表时间：
2007-01-23
影响因子：
11.1
通讯作者：
Sharan, Roded
中科院分区：
文献类型：
--
作者：
Tan, Kai;Shlomi, Tomer;Sharan, Roded
酵母双杂交和免疫共沉淀实验已经为许多模式生物确定了大规模的蛋白质 - 蛋白质相互作用网络。另外，系统性的染色质免疫沉淀实验使得转录调控相互作用的大型网络得以构建。为了研究这两种相互作用类型之间的功能相互关系，我们在一个概率框架内将两者结合起来，该框架将细胞建模为一个由转录因子调控蛋白质复合物的网络。这个框架在酵母中鉴定出72个假定的共调控复合物，并能够预测120种先前未被表征的转录相互作用。通过新的微阵列图谱对几个预测进行了测试，得到了与直接免疫沉淀实验相当的确认率（58%）。此外，我们将我们的框架扩展到跨物种环境，鉴定出24个在酵母和果蝇之间保守的共调控复合物。对这些保守复合物的分析揭示了它们的调控因子具有不同的保守水平，并提供了暗示性证据，即蛋白质 - 蛋白质相互作用网络可能比转录相互作用网络进化得更慢。我们的结果展示了如何将多种分子相互作用类型整合到细胞的全局连接图谱中，并且它们为蛋白质复合物调控的进化动力学提供了见解。
Yeast two-hybrid and coimmunoprecipitation experiments have defined large-scale protein-protein interaction networks for many model species. Separately, systematic chromatin immunoprecipitation experiments have enabled the assembly of large networks of transcriptional regulatory interactions. To investigate the functional interplay between these two interaction types, we combined both within a probabilistic framework that models the cell as a network of transcription factors regulating protein complexes. This framework identified 72 putative coregulated complexes in yeast and allowed the prediction of 120 previously uncharacterized transcriptional interactions. Several predictions were tested by new microarray profiles, yielding a confirmation rate (58%) comparable with that of direct immunoprecipitation experiments. Furthermore, we extended our framework to a cross-species setting, identifying 24 coregulated complexes that were conserved between yeast and fly. Analyses of these conserved complexes revealed different conservation levels of their regulators and provided suggestive evidence that protein-protein interaction networks may evolve more slowly than transcriptional interaction networks. Our results demonstrate how multiple molecular interaction types can be integrated toward a global wiring diagram of the cell, and they provide insights into the evolutionary dynamics of protein complex regulation.