G1/S Transcription Factor Copy Number Is a Growth-Dependent Determinant of Cell Cycle Commitment in Yeast
G1/S Transcription Factor Copy Number Is a Growth-Dependent Determinant of Cell Cycle Commitment in Yeast
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DOI：
10.1016/j.cels.2018.04.012
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发表时间：
2018-05-23
期刊：
影响因子：
9.3
通讯作者：
Royer, Catherine A.
中科院分区：
文献类型：
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作者：
Dorsey, Savanna;Tollis, Sylvain;Royer, Catherine A.
为了了解芽殖酵母细胞在G1期晚期(START)对细胞分裂的承诺是如何受生长和营养物质控制的，我们利用扫描数字和亮度(SN&B)显微镜测定了单个活酵母细胞中G1/S转录因子Sbf(由Swi4和Swi6组成)和MBF(由Mbp1和Swi6组成)、转录抑制因子Whi5和G1周期蛋白Cln1和Cln2的绝对浓度。在富培养液中，Whi5、Mbp1和Swi6的浓度与细胞大小无关，而Swi4的浓度在G1期增加一倍，导致Whi5/Swi4的比率随细胞大小的增加而降低。在小细胞中，SBF和MBF的拷贝数不足以饱和靶G1/S启动子，但随着细胞大小的增加，这种限制逐渐减弱。在较差的培养液中，SBF和MBF亚基以及Cln1均升高，与起始时较小的细胞尺寸一致。由SN&B数据约束的数学模型表明，SBF/MBF对G1/S启动子的大小和营养依赖的占据有助于设定启动激活的细胞大小阈值。
To understand how commitment to cell division in late G1 phase (Start) is controlled by growth and nutrients in budding yeast, we determined the absolute concentrations of the G1/S transcription factors SBF (composed of Swi4 and Swi6) and MBF (composed of Mbp1 and Swi6), the transcriptional repressor Whi5, and the G1 cyclins, Cln1 and Cln2, in single live yeast cells using scanning number and brightness (sN&B) microscopy. In rich medium, Whi5, Mbp1, and Swi6 concentrations were independent of cell size, whereas Swi4 concentration doubled in G1 phase, leading to a size-dependent decrease in the Whi5/Swi4 ratio. In small cells, SBF and MBF copy numbers were insufficient to saturate target G1/S promoters, but this restriction diminished as cells grew in size. In poor medium, SBF and MBF subunits, as well as Cln1, were elevated, consistent with a smaller cell size at Start. A mathematical model constrained by sN&B data suggested that size-and nutrient-dependent occupancy of G1/S promoters by SBF/MBF helps set the cell size threshold for Start activation.