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Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

机译:酵母中营养和应激调节基因的不同机制赋予其渐进控制和记忆

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Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.
机译:细胞通过对基因表达的精细调节来响应环境刺激。在这里,我们研究了响应酵母中营养和胁迫信号的高时间分辨率基因表达的剂量依赖性调节。细胞群中的 GAL1 活性在明确定义的半乳糖浓度范围内调节,与组蛋白重塑和RNA聚合酶II(RNAPII)关联的动态变化相关。此行为是由于整个种群中诱导剂浓度降低而导致的异构诱导延迟的结果。染色质重塑似乎是动态 GAL1 表达的基础,因为组蛋白动力学受损的突变体显示出严重的剂量反应曲线。相反, GRE2 启动子的运行就像快速的开/关开关,以响应不断增加的渗透压力,几乎恒定的表达速率,并且仅在时间上调节组蛋白重塑和RNAPII的占有率。 Gal3诱导剂和Hog1丝裂原激活蛋白(MAP)激酶似乎决定了两个启动子的不同剂量反应策略。因此,如果 GAL1 由于残留的Gal3水平而被预先刺激,则变得高度敏感并且不受剂量的影响,而 GRE2 的表达由于获得的抗逆性而在重复刺激后会减少。我们的分析揭示了动态信号创建剂量敏感基因表达输出方式的重要差异。

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