Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.
Curr Genet. 2019 Dec;65(6):1307-1312. doi: 10.1007/s00294-019-00992-w. Epub 2019 May 15.
Large numbers of eukaryotic transcription factors (TFs) are modified by SUMO post-translational modifications. Whereas the effect of TF sumoylation on the expression of target genes is largely context-dependent, it is not known whether the modification has a common function in regulating TFs throughout eukaryotic species. Here, I highlight four studies that used genome-wide chromatin-immunoprecipitation analysis (ChIP-seq) to examine whether sumoylation affects the selection of sites on the genome that are bound by human and yeast TFs. The studies found that impairing sumoylation led to deregulated binding-site selection for all four of the examined TFs. Predominantly, compared to wild-type forms, the sumoylation-deficient forms of the TFs bound to numerous additional non-specific sites, pointing to a common role for the modification in restricting TF binding to appropriate sites. Evidence from these studies suggests that TF sumoylation influences binding-site selection by modulating protein-protein interactions with other DNA-binding TFs, or by promoting conformational changes in the TFs that alter their DNA-binding specificity or affinity. I propose a model in which, prior to their sumoylation, TFs initially bind to chromatin with reduced specificity, which leads to spurious binding but also ensures that all functional sites become bound. Once the TFs are bound to DNA, sumoylation then acts to increase specificity and promotes release of the TFs from non-specific sites. The similar observations from these four genome-wide studies across divergent species suggest that binding-site selection is a general and conserved function for TF sumoylation.
大量真核转录因子 (TF) 受到 SUMO 翻译后修饰的影响。虽然 TF SUMO 化对靶基因表达的影响在很大程度上取决于具体情况，但尚不清楚该修饰是否在调节真核生物物种中的 TF 方面具有共同功能。在这里，我强调了四项使用全基因组染色质免疫沉淀分析 (ChIP-seq) 来研究 SUMO 化是否影响人类和酵母 TF 结合基因组上的靶位点选择的研究。这些研究发现，破坏 SUMO 化会导致所有四种被研究的 TF 的结合位点选择失调。主要是，与野生型形式相比，TF 的 SUMO 化缺陷形式与许多额外的非特异性位点结合，这表明该修饰在限制 TF 结合到适当的位点方面具有共同作用。这些研究的证据表明，TF SUMO 化通过调节与其他 DNA 结合 TF 的蛋白质-蛋白质相互作用，或通过促进 TF 的构象变化来改变其 DNA 结合特异性或亲和力，从而影响结合位点的选择。我提出了一个模型，即在 SUMO 化之前，TF 最初以降低特异性的方式与染色质结合，这导致了虚假的结合，但也确保了所有功能位点都被结合。一旦 TF 结合到 DNA 上，SUMO 化就会增加特异性并促进 TF 从非特异性位点释放。这四个来自不同物种的全基因组研究的相似观察结果表明，结合位点选择是 TF SUMO 化的一个普遍和保守的功能。
