G1/S transcription factors assemble in increasing numbers of discrete clusters through G1 phase
G1/S transcription factors assemble in increasing numbers of discrete clusters through G1 phase
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DOI：
10.1083/jcb.202003041
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发表时间：
2020-09-07
影响因子：
7.8
通讯作者：
Royer, Catherine Ann
中科院分区：
文献类型：
--
作者：
Black, Labe;Tollis, Sylvain;Royer, Catherine Ann
在芽殖酵母中，转录因子SBF和MBF在G1期晚期激活一个大的基因表达程序，该程序是细胞分裂的基础，称为启动。SBF/MBF对于小G1期细胞中的靶启动子是限制性的，并且随着细胞生长而积累，这提出了SBF/MBF如何在G1/S调节子中动态分布以及这如何影响Start转换的问题。超分辨率光激活定位显微镜（PALM）定位的静态位置的SBF/MBF亚基在固定的细胞揭示每个转录因子被组织成离散的集群，包含约8个拷贝，无论细胞大小，集群的总数增加细胞生长通过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的SBF/MBF聚类和预测TF动力学，在活细胞PALM实验中得到证实。SBF/MBF的这种时空组织可能有助于协调G1/S调节子和Start转换的激活。
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 spatiotemporal organization of SBF/MBF may help coordinate activation of G1/S regulon and the Start transition.