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Transcriptional response of steady-state yeast cultures to transient perturbations in carbon source

机译:稳态酵母培养物对碳源瞬时扰动的转录响应

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To understand the dynamics of transcriptional response to changing environments, well defined, easily controlled, and short-term perturbation experiments were undertaken. We subjected steady-state cultures of Saccharomyces cerevisiae in chemostats growing on limiting galactose to two different size pulses of glucose, well known to be a preferred carbon source. Although these pulses were not large enough to change growth rates or cell size, ≈ 25% of the genes changed their expression at least 2-fold. Using DNA microarrays to estimate mRNA abundance, we found a number of distinguishable patterns of transcriptional response among the many genes whose expression changed. Many of these genes were already known to be regulated by particular transcription factors; we estimated five potentially relevant transcription factor activities from the observed changes in gene expression (i.e., Mig1p, Gal4p, Cat8p, Rgt1p, Adr1p, and Rcs1p). With these estimates, for two regulatory circuits involving interaction among multiple regulators we could generate dynamical models that quantitatively account for the observed transcriptional responses to the transient perturbations.
机译:为了了解转录对变化的环境的动态变化,进行了定义明确,易于控制和短期扰动的实验。我们在恒化器中进行了酿酒酵母的稳态培养,该恒化器中的半乳糖限制为两个不同大小的葡萄糖脉冲,众所周知这是一种优选的碳源。尽管这些脉冲的大小不足以改变生长速率或细胞大小,但≈25%的基因改变了其表达至少2倍。使用DNA芯片估计mRNA的丰度,我们发现了许多表达发生变化的基因之间转录反应的许多可区分模式。已知其中许多基因受特定转录因子的调控。我们从观察到的基因表达变化(即Mig1p,Gal4p,Cat8p,Rgt1p,Adr1p和Rcs1p)估计了五种可能相关的转录因子活性。通过这些估计,对于涉及多个调节器之间相互作用的两个调节电路,我们可以生成动力学模型,该模型定量地解释了观察到的对瞬时扰动的转录反应。

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