Genome-wide transcriptional plasticity underlies cellular adaptation to novel challenge
Genome-wide transcriptional plasticity underlies cellular adaptation to novel challenge
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DOI：
10.1038/msb4100147
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发表时间：
2007-04-01
影响因子：
9.9
通讯作者：
Braun, Erez
中科院分区：
文献类型：
--
作者：
Stern, Shay;Dror, Tali;Braun, Erez
细胞调整其转录状态以适应环境和遗传干扰。一个悬而未决的问题是，在多大程度上转录响应扰动已被专门选择沿着进化。为了测试转录重编程不需要“预先设计”以在生理时间尺度上导致适应性代谢状态的可能性，我们让酵母细胞面临他们以前从未遇到过的新挑战。我们通过从组氨酸生物合成途径中招募一个必需基因HIS3，将基因组重新连接到一个外源调控系统，即负责半乳糖利用的GAL网络。在恒化器中将培养基切换为葡萄糖引起必需基因的抑制，并使细胞面临严峻的挑战，它们适应了大约10代。使用全基因组表达阵列，我们在这里表明，全球转录重编程（> 1200个基因）的适应。在重复实验中，很大一部分响应基因是不可重现的。这些结果表明，非特异性转录反应反映了调节网络的天然可塑性，支持细胞适应新的挑战。
Cells adjust their transcriptional state to accommodate environmental and genetic perturbations. An open question is to what extent transcriptional response to perturbations has been specifically selected along evolution. To test the possibility that transcriptional reprogramming does not need to be 'pre-designed' to lead to an adaptive metabolic state on physiological timescales, we confronted yeast cells with a novel challenge they had not previously encountered. We rewired the genome by recruiting an essential gene, HIS3, from the histidine biosynthesis pathway to a foreign regulatory system, the GAL network responsible for galactose utilization. Switching medium to glucose in a chemostat caused repression of the essential gene and presented the cells with a severe challenge to which they adapted over approximately 10 generations. Using genome-wide expression arrays, we show here that a global transcriptional reprogramming (> 1200 genes) underlies the adaptation. A large fraction of the responding genes is nonreproducible in repeated experiments. These results show that a nonspecific transcriptional response reflecting the natural plasticity of the regulatory network supports adaptation of cells to novel challenges.