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G1/S transcription factors assemble in increasing numbers of discrete clusters through G1 phase
The Journal of Cell Biology Pub Date : 2020-08-03 , DOI: 10.1083/jcb.202003041
Labe Black 1 , Sylvain Tollis 2 , Guo Fu 1 , Jean-Bernard Fiche 3 , Savanna Dorsey 1 , Jing Cheng 2 , Ghada Ghazal 2 , Stephen Notley 1 , Benjamin Crevier 1 , Jeremy Bigness 1 , Marcelo Nollmann 3 , Mike Tyers 2 , Catherine Ann Royer 1
Affiliation  

In budding yeast, the transcription factors SBF and MBF activate a large program of gene expression in late G1 phase that underlies commitment to cell division, termed Start. SBF/MBF are limiting with respect to target promoters in small G1 phase cells and accumulate as cells grow, raising the questions of how SBF/MBF are dynamically distributed across the G1/S regulon and how this impacts the Start transition. Super-resolution Photo-Activatable Localization Microscopy (PALM) mapping of the static positions of SBF/MBF subunits in fixed cells revealed each transcription factor was organized into discrete clusters containing approximately eight copies regardless of cell size and that the total number of clusters increased as cells grew through G1 phase. Stochastic modeling using reasonable biophysical parameters recapitulated growth-dependent SBF/MBF clustering and predicted TF dynamics that were confirmed in live cell PALM experiments. This spatio-temporal organization of SBF/MBF may help coordinate activation of G1/S regulon and the Start transition.

中文翻译:

G1/S 转录因子在 G1 期以越来越多的离散簇组装

在芽殖酵母中,转录因子 SBF 和 MBF 在 G1 期晚期激活一个大型基因表达程序,该程序是细胞分裂承诺的基础,称为“启动”。SBF/MBF 相对于小 G1 期细胞中的目标启动子是有限的,并且随着细胞生长而积累,这就提出了 SBF/MBF 如何在 G1/S 调节子中动态分布以及这如何影响起始转变的问题。固定细胞中 SBF/MBF 亚基静态位置的超分辨率光激活定位显微镜 (PALM) 绘图显示,每个转录因子被组织成包含大约 8 个拷贝的离散簇,无论细胞大小如何,并且簇总数随着细胞生长至G1期。使用合理的生物物理参数的随机建模概括了生长依赖性 SBF/MBF 聚类并预测了 TF 动态,这在活细胞 PALM 实验中得到了证实。SBF/MBF 的这种时空组织可能有助于协调 G1/S 调节子的激活和起始转换。
更新日期:2020-08-03
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