A fine kinetic balance of interactions directs transcription factor hubs to genes.
A fine kinetic balance of interactions directs transcription factor hubs to genes.
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相互作用的良好动力学平衡将转录因子中枢引导至基因。
DOI：
10.1101/2024.04.16.589811
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Mir,Mustafa
中科院分区：
文献类型：
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作者：
Mukherjee,Apratim;Fallacaro,Samantha;Ratchasanmuang,Puttachai;Zinski,Joseph;Boka,Alan;Shankta,Kareena;Mir,Mustafa
真核基因调控依赖于序列特异性转录因子（TF）的结合。TF短暂结合染色质，但通过形成增加结合频率的高局部浓度微环境（枢纽和浓缩物）来占据其靶位点。尽管它们普遍存在，但由于技术限制，这种微环境很难在内源性背景下进行研究。在这里，我们使用活胚胎光片成像，单分子跟踪和基因组学来克服这些限制，并研究枢纽如何定位于靶基因以驱动TF占用和转录。通过研究突变体的枢纽形成TF，塞尔达，在果蝇胚胎中，我们发现枢纽形成倾向，空间分布和时间稳定性的差异调节DNA结合和无序的蛋白质结构域。我们发现，枢纽定位到基因组靶点是由蛋白质和染色质之间相互作用的微调动力学平衡驱动的，当这种平衡受到干扰时，枢纽可以被重定向到新的基因组位点。
Eukaryotic gene regulation relies on the binding of sequence-specific transcription factors (TFs). TFs bind chromatin transiently yet occupy their target sites by forming high-local concentration microenvironments (hubs and condensates) that increase the frequency of binding. Despite their ubiquity, such microenvironments are difficult to study in endogenous contexts due to technical limitations. Here, we use live embryo light-sheet imaging, single-molecule tracking, and genomics to overcome these limitations and investigate how hubs are localized to target genes to drive TF occupancy and transcription. By examining mutants of a hub-forming TF, Zelda, in Drosophila embryos, we find that hub formation propensity, spatial distributions, and temporal stabilities are differentially regulated by DNA binding and disordered protein domains. We show that hub localization to genomic targets is driven by a finely-tuned kinetic balance of interactions between proteins and chromatin, and hubs can be redirected to new genomic sites when this balance is perturbed.