A biophysical model of supercoiling dependent transcription predicts a structural aspect to gene regulation.
A biophysical model of supercoiling dependent transcription predicts a structural aspect to gene regulation.
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超涂层依赖转录的生物物理模型预测了基因调节的结构方面。
DOI：
10.1186/s13628-016-0027-0
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Roberts E
中科院分区：
文献类型：
--
作者：
Bohrer CH;Roberts E
大肠杆菌中的转录在DNA中产生正超螺旋，其被促旋酶的酶活性所缓解。最近发表的实验证据表明，转录起始和延伸被抑制的建设积极超螺旋。因此，有人提出促旋酶的间歇性结合在转录爆发中起作用。考虑到转录是最基本的细胞过程之一，期望能够解释转录模型中正超螺旋的积累和释放。在这里，我们提出了一个详细的基因表达生物物理模型，其中纳入了转录引起的超螺旋效应。通过将正超螺旋的量与转录速率直接联系起来，该模型预测高度转录的基因的mRNA分布应该基本上偏离泊松分布，在低mRNA拷贝数下具有增强的密度。此外，该模型预测了同一超螺旋结构域内基因表达水平之间的高度相关性。我们的模型结合了基因的超螺旋状态，做出了不同于以前基因表达模型的具体预测。同一超螺旋结构域中的基因影响相邻基因的表达水平。这种结构依赖性调控预测了同一超螺旋结构域中基因之间的相关性。因此，染色体的拓扑结构创造了更高水平的基因调控，这对理解细菌基因组的进化和组织具有广泛的意义。本文的在线版本（doi：10.1186/s13628-016-0027-0）包含补充材料，可供授权用户使用。
Transcription in Escherichia coli generates positive supercoiling in the DNA, which is relieved by the enzymatic activity of gyrase. Recently published experimental evidence suggests that transcription initiation and elongation are inhibited by the buildup of positive supercoiling. It has therefore been proposed that intermittent binding of gyrase plays a role in transcriptional bursting. Considering that transcription is one of the most fundamental cellular processes, it is desirable to be able to account for the buildup and release of positive supercoiling in models of transcription. Here we present a detailed biophysical model of gene expression that incorporates the effects of supercoiling due to transcription. By directly linking the amount of positive supercoiling to the rate of transcription, the model predicts that highly transcribed genes’ mRNA distributions should substantially deviate from Poisson distributions, with enhanced density at low mRNA copy numbers. Additionally, the model predicts a high degree of correlation between expression levels of genes inside the same supercoiling domain. Our model, incorporating the supercoiling state of the gene, makes specific predictions that differ from previous models of gene expression. Genes in the same supercoiling domain influence the expression level of neighboring genes. Such structurally dependent regulation predicts correlations between genes in the same supercoiling domain. The topology of the chromosome therefore creates a higher level of gene regulation, which has broad implications for understanding the evolution and organization of bacterial genomes. The online version of this article (doi:10.1186/s13628-016-0027-0) contains supplementary material, which is available to authorized users.