PDF(Pubmed)
Abstract：
During development cells receive a variety of signals, which are of crucial importance to their fate determination. One such source of signal is the Notch signalling pathway, where Notch activity regulates expression of target genes through the core transcription factor CSL. To understand changes in transcription factor behaviour that lead to transcriptional changes in Notch active cells, we have probed CSL behaviours in real time, using in vivo Single Molecule Localisation Microscopy. Trajectory analysis reveals that Notch-On conditions increase the fraction of bound CSL molecules, but also the proportion of molecules with exploratory behaviours. These properties are shared by the co-activator Mastermind. Furthermore, both CSL and Mastermind, exhibit characteristics of local exploration near a Notch target locus. A similar behaviour is observed for CSL molecules diffusing in the vicinity of other bound CSL clusters. We suggest therefore that CSL acquires an exploratory behaviour when part of the activation complex, favouring local searching and retention close to its target enhancers. This change explains how CSL can efficiently increase its occupancy at target sites in Notch-On conditions.
摘要：
在发育过程中，细胞接收各种信号，这对他们的命运决定至关重要。一个这样的信号源是Notch信号通路，其中Notch活性通过核心转录因子CSL调节靶基因的表达。为了了解导致Notch活性细胞转录变化的转录因子行为的变化，我们实时调查了CSL行为，使用体内单分子定位显微镜。轨迹分析表明，Notch-On条件增加了结合CSL分子的分数，还有具有探索行为的分子的比例。这些属性由协同激活者Mastermind共享。此外，CSL和Mastermind,在Notch目标位点附近表现出局部勘探的特征。对于在其他结合的CSL簇附近扩散的CSL分子，观察到类似的行为。因此，我们建议CSL在激活复合物的一部分时获得探索性行为，有利于接近其目标增强子的本地搜索和保留。此更改说明了CSL如何在Notch-On条件下有效地增加其在目标站点的占用。
