Spo0A~P imposes a temporal gate for the bimodal expression of competence in Bacillus subtilis.
Spo0A~P imposes a temporal gate for the bimodal expression of competence in Bacillus subtilis.
复制标题
DOI：
10.1371/journal.pgen.1002586
复制
发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Dubnau D
中科院分区：
文献类型：
--
作者：
Mirouze N;Desai Y;Raj A;Dubnau D
ComK在转录上控制枯草芽孢杆菌中转化DNA的摄取能力。克隆群体中只有10%-20%的细胞被随机选择用于感受态。由于ComK激活其自身的启动子，超过ComK阈值量的细胞触发正反馈回路，转变为感受态ON状态。过渡速率在接近稳定期期间增加到最大值，然后降低，大多数细胞保持关闭。comK转录的平均基础速率瞬时增加，定义了转换的机会窗口，并解释了主管群体的异质性。我们表明，作为响应调节剂Spo 0A的浓度增加，在进入稳定期，它首先诱导comK启动子活性，然后抑制它通过直接结合。Spo 0A通过拮抗阻遏物Rok激活Spo 0A。这放大了在接近稳定期期间发生的基础水平comK启动子活性的固有增加，并且是核心启动子的一般特征，用于将感受态转变的概率与生长速率相结合。因此，竞争力的转变是由生长速度和时间控制的复杂机制，管理Spo 0A的形成。在单个细胞的水平上，决定命运的噪音是comK启动子固有的。这一整体机制已被随机模拟，并显示是合理的。因此，一个确定性的机制调节一个固有的随机过程。细菌细胞的群体有时会分成具有不同基因表达模式的亚群。土壤细菌B.枯草杆菌变得“有能力”吸收环境DNA，从而获得新的遗传信息。通过comK转录的随机波动选择约15%的细胞用于表达感受态基因。当ComK的浓度超过临界阈值时，它会激活自己的表达，一个分子开关被抛出，并在该细胞中增强能力。在这里，我们要问为什么所有的细胞最终都没有打开开关。我们发现，comK的基础水平表达增加，然后随着营养物质的耗尽而减少，因此超过ComK阈值的细胞数量上升和福尔斯下降，打开和关闭了一个竞争力的机会窗口。导致comK表达“上升”的两个因素是：1）随着细胞分裂减慢，转录的整体增加，以及2）主调节蛋白Spo 0A-P的浓度持续上升，其激活并随后在积累时抑制comK。全局增加传递生长速率信息，Spo 0A β P的增加编码多个信号，包括培养物的营养、复制和种群密度状态。
ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%–20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A∼P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A∼P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A∼P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process. Populations of bacterial cells sometimes bifurcate into subpopulations with different patterns of gene expression. The soil bacterium B. subtilis becomes “competent” for the uptake of environmental DNA, thus acquiring new genetic information. About 15% of the cells are chosen for expression of the competence genes by stochastic fluctuations in the transcription of comK. When the concentration of ComK exceeds a critical threshold, it activates its own expression, a molecular switch is thrown, and competence ensues in that cell. Here we ask why all of the cells do not eventually throw the switch. We show that the basal level expression of comK increases and then decreases as nutrients are exhausted, so that the number of cells exceeding the ComK threshold rises and falls, opening and closing a window of opportunity for competence. Two factors responsible for this “uptick” in comK expression are: 1) a global increase in transcription as cell division slows, and 2) a continual rise in the concentration of the master regulatory protein Spo0A-P, which activates and then represses comK as it accumulates. The global increase transmits growth rate information and the increase in Spo0A∼P encodes multiple signals, including the nutritional, replication, and population density status of the culture.
登录
查看更多内容
影响因子：
64.5
作者：
BURBULYS, D;TRACH, KA;HOCH, JA
通讯作者：
HOCH, JA
影响因子：
56.9
作者：
Maamar, Hedia;Raj, Arjun;Dubnau, David
通讯作者：
Dubnau, David
DOI：
10.1073/pnas.1002499107
发表时间：
2010-05-04
影响因子：
11.1
作者：
Chastanet, Arnaud;Vitkup, Dennis;Losick, Richard M.
通讯作者：
Losick, Richard M.
影响因子：
11.4
作者：
Chai, Yunrong;Norman, Thomas;Losick, Richard
通讯作者：
Losick, Richard
影响因子：
3.6
作者：
Maamar, H;Dubnau, D
通讯作者：
Dubnau, D