Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell Syst. 2023 Sep 20;14(9):732-745.e5. doi: 10.1016/j.cels.2023.06.010. Epub 2023 Jul 31.
The binding of transcription factors (TFs) along genomes is restricted to a subset of sites containing their preferred motifs. TF-binding specificity is often attributed to the co-binding of interacting TFs; however, apart from specific examples, this model remains untested. Here, we define dependencies among budding yeast TFs that localize to overlapping promoters by profiling the genome-wide consequences of co-depleting multiple TFs. We describe unidirectional interactions, revealing Msn2 as a central factor allowing TF binding at its target promoters. By contrast, no case of mutual cooperation was observed. Particularly, Msn2 retained binding at its preferred promoters upon co-depletion of fourteen similarly bound TFs. Overall, the consequences of TF co-depletions were moderate, limited to a subset of promoters, and failed to explain the role of regions outside the DNA-binding domain in directing TF-binding preferences. Our results call for re-evaluating the role of cooperative interactions in directing TF-binding preferences.
转录因子（TFs）沿着基因组的结合被限制在包含其首选基序的亚组位点上。TF 结合的特异性通常归因于相互作用的 TFs 的共同结合；然而，除了特定的例子之外，这个模型尚未经过测试。在这里，我们通过分析多个 TF 共耗竭对全基因组的影响，定义了定位于重叠启动子的酿酒酵母 TFs 之间的依赖性。我们描述了单向相互作用，揭示了 Msn2 作为一个中央因素，允许 TF 在其靶启动子上结合。相比之下，没有观察到相互合作的情况。特别是，在共耗竭 14 个同样结合的 TF 后，Msn2 仍然在其首选启动子上保留了结合。总的来说，TF 共耗竭的结果是适度的，仅限于一组启动子，并且不能解释 DNA 结合域以外的区域在指导 TF 结合偏好方面的作用。我们的结果呼吁重新评估合作相互作用在指导 TF 结合偏好方面的作用。
