Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Cell Rep. 2019 Apr 16;27(3):955-970.e7. doi: 10.1016/j.celrep.2019.03.071.
Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. We combined our interactome with prior PPI data to generate an integrated Drosophila TF-TF binary interaction network. Our analysis of ChIP-seq data, integrating PPI and gene expression information, uncovered different modes by which interacting TFs are recruited to DNA. We further demonstrate the utility of our Drosophila interactome in shedding light on human TF-TF interactions. This study reveals how TFs interact to bind regulatory elements in vivo and serves as a resource of Drosophila TF-TF binary PPIs for understanding tissue-specific gene regulation.
转录因子（TFs）之间的组合相互作用在多细胞生物中产生基因表达特异性和多样性方面发挥着重要作用。我们使用酵母双杂交（Y2H）实验对几乎所有序列特异性果蝇 TF 进行了检测，鉴定出 1983 种蛋白质-蛋白质相互作用（PPIs），使目前已知的果蝇 TF 之间的 PPIs 数量增加了一倍以上。为了进行质量评估，我们使用 MITOMI 和双分子荧光互补测定法验证了我们的部分相互作用。我们将互作组与之前的 PPI 数据相结合，生成了一个整合的果蝇 TF-TF 二元相互作用网络。我们通过整合 PPI 和基因表达信息对 ChIP-seq 数据进行了分析，揭示了相互作用的 TF 结合 DNA 的不同模式。我们进一步证明了我们的果蝇互作组在揭示人类 TF-TF 相互作用方面的有用性。这项研究揭示了 TFs 如何在体内相互作用以结合调节元件，并为理解组织特异性基因调控提供了一个用于研究果蝇 TF-TF 二元 PPIs 的资源。
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