Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae.

Growth-rate regulated genes have profound impact on interpretation of transcriptome profiling in Saccharomyces cerevisiae.
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DOI:
10.1186/gb-2006-7-11-r107
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发表时间:
2006
期刊:
影响因子:
12.3
通讯作者:
Nielsen J
Nielsen J
中科院分区:
生物学1区
文献类型:
--
作者:
Regenberg B;Grotkjaer T;Winther O;Fausbøll A;Akesson M;Bro C;Hansen LK;Brunak S;Nielsen J

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分析S.具有在2和35小时之间变化的世代时间的酿酒酵母培养物表明,所有酵母基因的一半的表达受比生长速率的影响。生长速度是所有生物体细胞发育的核心。然而,人们对增长率变化的影响知之甚少。我们使用连续培养来控制生长速率,并研究了真核生物酿酒酵母模型的转录程序,其世代时间在2至35小时之间变化。共5930个成绩单被确定在不同的增长率研究。这些的共识聚类显示,所有酵母基因中有一半受到特定生长速率的影响,并且这些变化与细胞暴露于不同类型的应激时发现的变化相似(>80%重叠)。响应于更快的生长而具有降低的转录水平的基因在很大程度上具有未知的功能(>50%),而具有增加的转录水平的基因参与大分子生物合成,例如编码核糖体蛋白的那些。该组还涵盖了转录激活因子RAP 1的大多数靶点,已知RAP 1也参与复制。复制起点的位置和生长调节基因的位置之间的正相关性表明复制在生长速率调节中的作用。我们的数据表明,细胞生长速率对转录调控有很大的影响。这反过来又意味着在比较具有不同生长速率的突变体时应该谨慎。我们的研究结果还表明,大部分的调节是通过受影响的基因,这可能是有价值的信息,在代谢工程中的异源基因表达的控制染色体定位协调。
Analysis of S. cerevisiae cultures with generation times varying between 2 and 35 hours shows that the expression of half of all yeast genes is affected by the specific growth rate. Growth rate is central to the development of cells in all organisms. However, little is known about the impact of changing growth rates. We used continuous cultures to control growth rate and studied the transcriptional program of the model eukaryote Saccharomyces cerevisiae, with generation times varying between 2 and 35 hours. A total of 5930 transcripts were identified at the different growth rates studied. Consensus clustering of these revealed that half of all yeast genes are affected by the specific growth rate, and that the changes are similar to those found when cells are exposed to different types of stress (>80% overlap). Genes with decreased transcript levels in response to faster growth are largely of unknown function (>50%) whereas genes with increased transcript levels are involved in macromolecular biosynthesis such as those that encode ribosomal proteins. This group also covers most targets of the transcriptional activator RAP1, which is also known to be involved in replication. A positive correlation between the location of replication origins and the location of growth-regulated genes suggests a role for replication in growth rate regulation. Our data show that the cellular growth rate has great influence on transcriptional regulation. This, in turn, implies that one should be cautious when comparing mutants with different growth rates. Our findings also indicate that much of the regulation is coordinated via the chromosomal location of the affected genes, which may be valuable information for the control of heterologous gene expression in metabolic engineering.
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