Transcription factors play an essential role in pattern formation during early embryo development, generating a strikingly fast and precise transcriptional response that results in sharp gene expression boundaries. To characterize the steps leading up to transcription, we performed a side-by-side comparison of the nuclear dynamics of two morphogens, a transcriptional activator, Bicoid (Bcd), and a transcriptional repressor, Capicua (Cic), both involved in body patterning along the anterior-posterior axis of the early embryo. We used a combination of fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single-particle tracking to access a wide range of dynamical timescales. Despite their opposite effects on gene transcription, we find that Bcd and Cic have very similar nuclear dynamics, characterized by the coexistence of a freely diffusing monomer population with a number of oligomeric clusters, which range from low stoichiometry and high mobility clusters to larger, DNA-bound hubs. Our observations are consistent with the inclusion of both Bcd and Cic into transcriptional hubs or condensates, while putting constraints on the mechanism by which these form. These results fit in with the recent proposal that many transcription factors might share a common search strategy for target gene regulatory regions that makes use of their large unstructured regions, and may eventually help explain how the transcriptional response they elicit can be at the same time so fast and so precise.

中文翻译：

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转录激活因子 Bcd 和阻遏因子 Cic 均形成小的可移动寡聚簇


转录因子在早期胚胎发育过程中的模式形成中发挥着重要作用，产生极其快速和精确的转录反应，从而产生清晰的基因表达边界。为了表征转录前的步骤，我们对两种形态发生素、转录激活因子 Bicoid (Bcd) 和转录抑制因子 Capicua (Cic) 的核动力学进行了并排比较，这两种形态素均参与身体模式形成沿着早期胚胎的前后轴。我们结合使用光漂白后的荧光恢复、荧光相关光谱和单粒子跟踪来获得广泛的动态时间尺度。尽管它们对基因转录的影响相反，我们发现 Bcd 和 Cic 具有非常相似的核动力学，其特征是自由扩散的单体群体与许多寡聚簇共存，这些寡聚簇的范围从低化学计量和高迁移率簇到更大的 DNA绑定枢纽。我们的观察结果与 Bcd 和 Cic 都包含在转录中心或缩合物中是一致的，同时对它们的形成机制施加了限制。这些结果符合最近的提议，即许多转录因子可能共享一个共同的目标基因调控区域搜索策略，利用其大的非结构化区域，并最终可能有助于解释它们如何同时引起转录反应快速且精确。