Surprising connections between DNA binding and function for the near-complete set of yeast transcription factors [ChEC-seq]

DNA sequence-specific transcription factors (TFs) modulate transcription and chromatin architecture, acting from regulatory sites in enhancers and promoters of eukaryotic genes. How TFs locate their DNA targets and how multiple TFs cooperate to regulate individual genes is still unclear. Most yeast TFs are thought to regulate transcription via binding to upstream activating sequences, situated within a few hundred base pairs upstream of the regulated gene. While this model has been validated for individual TFs and specific genes, it has not been tested in a systematic way with the large set of yeast TFs. Here, we have integrated information on the binding and expression targets for the near-complete set of yeast TFs. While we found many instances of functional TF binding sites in upstream regulatory regions, we found many more instances that do not fit this model. In many cases, we find that rapid TF depletion affects gene expression where there is no detectable binding of that TF to the upstream region of the affected gene. We also found that, for most TFs, only a small fraction of bound TFs regulates the nearby gene, showing that TF binding does not automatically correspond to regulation of the linked gene. Overall, our comprehensive mapping of TF binding and regulatory targets have both confirmed known TF relationships and revealed surprising properties of TF function.DNA序列特异性转录因子（transcription factors, TFs）可调控转录与染色质结构，通过结合真核基因增强子与启动子区域的调控位点发挥作用。目前学界尚未明确TFs如何定位其DNA靶点，以及多个TFs如何协同调控单个基因。多数酵母TF被认为通过结合调控基因上游数百碱基对范围内的上游激活序列（upstream activating sequences）来调控转录。尽管该模型已在单个TF与特定基因中得到验证，但尚未针对全部酵母TF开展系统性检验。本研究整合了近乎完整的酵母TF全集的结合与表达靶点信息。研究中，我们不仅在上游调控区域发现了大量功能性TF结合位点，同时也观测到更多不符合该模型的案例。在诸多情形下，即便靶基因上游区域未检测到对应TF的结合，该TF的快速耗竭仍会影响靶基因的表达。此外我们还发现，对于大多数TF而言，仅有极小部分结合的TF会调控其邻近基因，这表明TF结合并不会自动对应至其所关联基因的调控过程。总体而言，我们对TF结合与调控靶点的全面定位，既验证了已知的TF调控关系，也揭示了TF功能中诸多令人意外的新特性。