Remaud Sylvie, Audibert Agnès, Gho Michel
Université Pierre et Marie Curie, UMR 7622, Paris, France.
PLoS One. 2008;3(11):e3646. doi: 10.1371/journal.pone.0003646. Epub 2008 Nov 5.
We have studied cell sensitivity to Notch pathway signalling throughout the cell cycle. As model system, we used the Drosophila bristle lineage where at each division N plays a crucial role in fate determination. Using in vivo imaging, we followed this lineage and activated the N-pathway at different moments of the secondary precursor cell cycle. We show that cells are more susceptible to respond to N-signalling during the S-phase. Thus, the period of heightened sensitivity coincided with the period of the S-phase. More importantly, modifications of S-phase temporality induced corresponding changes in the period of the cell's reactivity to N-activation. Moreover, S-phase abolition was correlated with a decrease in the expression of tramtrack, a downstream N-target gene. Finally, N cell responsiveness was modified after changes in chromatin packaging. We suggest that high-order chromatin structures associated with the S-phase create favourable conditions that increase the efficiency of the transcriptional machinery with respect to N-target genes.
我们研究了细胞在整个细胞周期中对Notch信号通路的敏感性。作为模型系统，我们使用了果蝇刚毛谱系，在每次细胞分裂时，Notch（N）在命运决定中起着关键作用。通过体内成像，我们追踪了这个谱系，并在次级前体细胞周期的不同时刻激活N信号通路。我们发现细胞在S期对N信号的反应更敏感。因此，敏感性增强的时期与S期一致。更重要的是，S期时间性的改变会引起细胞对N激活反应期的相应变化。此外，S期缺失与N下游靶基因tramtrack的表达降低相关。最后，染色质包装改变后，N细胞反应性也发生了改变。我们认为，与S期相关的高阶染色质结构创造了有利条件，提高了转录机制针对N靶基因的效率。
