To predict transcription, one needs a mechanistic understanding of how the numerous required transcription factors (TFs) explore the nuclear space to find their target genes, assemble, cooperate, and compete with one another. Advances in fluorescence microscopy have made it possible to visualize real-time TF dynamics in living cells, leading to two intriguing observations: first, most TFs contact chromatin only transiently; and second, TFs can assemble into clusters through their intrinsically disordered regions. These findings suggest that highly dynamic events and spatially structured nuclear microenvironments might play key roles in transcription regulation that are not yet fully understood. The emerging model is that while some promoters directly convert TF-binding events into on/off cycles of transcription, many others apply complex regulatory layers that ultimately lead to diverse phenotypic outputs. Cracking this kinetic code is an ongoing and challenging task that is made possible by combining innovative imaging approaches with biophysical models.

中文翻译：

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转录因子动力学

为了预测转录，需要从机制上理解众多必需的转录因子 (TF) 如何探索核空间以找到其靶基因、组装、合作以及相互竞争。荧光显微镜的进步使得活细胞中实时 TF 动态可视化成为可能，从而产生了两个有趣的观察结果：首先，大多数 TF 仅短暂接触染色质；其次，转录因子可以通过其本质上无序的区域组装成簇。这些发现表明，高度动态的事件和空间结构的核微环境可能在转录调控中发挥着尚未完全理解的关键作用。新兴的模型是，虽然一些启动子直接将 TF 结合事件转化为转录的开/关循环，但许多其他启动子应用复杂的调控层，最终导致不同的表型输出。破解这一动力学密码是一项持续且具有挑战性的任务，通过将创新成像方法与生物物理模型相结合使之成为可能。