Regulatory consequences of gene translocation in bacteria.

Regulatory consequences of gene translocation in bacteria.
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细菌基因易位的调控后果。

DOI:
10.1093/nar/gks694
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发表时间:
2012-10
影响因子:
14.9
通讯作者:
Lim HN
Lim HN
中科院分区:
生物学2区
文献类型:
--
作者:
Block DH;Hussein R;Liang LW;Lim HN

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基因易位在细菌基因组的可塑性和进化中起着重要作用。在这项研究中,我们研究了三个基因组组织特征对基因调控的影响,这些特征可以通过易位改变:(i)染色体位置;(ii)基因方向;(iii)靶基因与其转录因子基因之间的距离(“靶TF距离”)。具体而言,我们量化的组成型表达,转录因子结合和/或基因表达噪音,在大肠杆菌中使用的合成网络组成的转录因子(LacI阻遏物)和其靶基因(yfp)的这些功能的效果。在这里,我们表明,基因调控通常是强大的染色体位置,基因方向和目标TF距离的变化。唯一可证实的效应是染色体位置改变组成型表达,这是由于基因拷贝数和局部序列效应的变化,并且这决定了最大和最小表达水平。结果被纳入一个数学模型,该模型用于定量预测一个简单的基因网络对基因易位的反应;实验证实了预测。总之,基因易位可以调节组成型基因的表达水平,由于染色体位置的变化,但它对基因调控的其他方面的影响很小。
Gene translocations play an important role in the plasticity and evolution of bacterial genomes. In this study, we investigated the impact on gene regulation of three genome organizational features that can be altered by translocations: (i) chromosome position; (ii) gene orientation; and (iii) the distance between a target gene and its transcription factor gene (‘target-TF distance’). Specifically, we quantified the effect of these features on constitutive expression, transcription factor binding and/or gene expression noise using a synthetic network in Escherichia coli composed of a transcription factor (LacI repressor) and its target gene (yfp). Here we show that gene regulation is generally robust to changes in chromosome position, gene orientation and target-TF distance. The only demonstrable effect was that chromosome position alters constitutive expression, due to changes in gene copy number and local sequence effects, and that this determines maximum and minimum expression levels. The results were incorporated into a mathematical model which was used to quantitatively predict the responses of a simple gene network to gene translocations; the predictions were confirmed experimentally. In summary, gene translocation can modulate constitutive gene expression levels due to changes in chromosome position but it has minimal impact on other facets of gene regulation.
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期刊: BIOCHEMISTRY
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发表时间: 2008-10-17
期刊: Science (New York, N.Y.)
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