Transcriptional regulation shapes the organization of genes on bacterial chromosomes.

Transcriptional regulation shapes the organization of genes on bacterial chromosomes.
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DOI:
10.1093/nar/gkp231
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发表时间:
2009-06
影响因子:
14.9
通讯作者:
Martínez-Antonio A
Martínez-Antonio A
中科院分区:
生物学2区
文献类型:
--
作者:
Janga SC;Salgado H;Martínez-Antonio A

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转录因子(TF)是负责控制细菌基因组中基因表达的关键元件,当在基因组规模上可视化时,它们之间以及与其他蛋白质编码基因之间形成密集的转录相互作用网络。尽管转录调控网络(TRN)的结构已广为人知,但尚不清楚它们受哪些约束。在这里,我们使用模型原核生物的 TRN 来探索这个问题,并提供调节子的转录层次结构与其基因组组织之间的联系。我们表明,为了驱动动力学和浓度梯度,属于大调节子和小调节子的转录因子,根据它们调节的基因数量,在基因组上根据其靶标进行不同的组织。然后,我们提出了一个概念模型,可以解释 TRN 的层次结构最终如何受 TF 靶向 DNA 结合位点的动态生物物理要求的控制。我们的结果表明,定义转录因子在网络层次结构中位置的主要参数是它们调节的基因的数量和染色体距离以及它们的蛋白质浓度梯度。这些观察结果让我们深入了解转录网络的层次结构如何在染色体上编码,以驱动转录因子的动力学和浓度梯度,具体取决于它们调节的基因数量,并且可能是其他原核生物有效的共同主题,提出了转录调控在塑造染色体上基因组织中的作用。
Transcription factors (TFs) are the key elements responsible for controlling the expression of genes in bacterial genomes and when visualized on a genomic scale form a dense network of transcriptional interactions among themselves and with other protein coding genes. Although the structure of transcriptional regulatory networks (TRNs) is well understood, it is not clear what constrains govern them. Here, we explore this question using the TRNs of model prokaryotes and provide a link between the transcriptional hierarchy of regulons and their genome organization. We show that, to drive the kinetics and concentration gradients, TFs belonging to big and small regulons, depending on the number of genes they regulate, organize themselves differently on the genome with respect to their targets. We then propose a conceptual model that can explain how the hierarchical structure of TRNs might be ultimately governed by the dynamic biophysical requirements for targeting DNA-binding sites by TFs. Our results suggest that the main parameters defining the position of a TF in the network hierarchy are the number and chromosomal distances of the genes they regulate and their protein concentration gradients. These observations give insights into how the hierarchical structure of transcriptional networks can be encoded on the chromosome to drive the kinetics and concentration gradients of TFs depending on the number of genes they regulate and could be a common theme valid for other prokaryotes, proposing the role of transcriptional regulation in shaping the organization of genes on a chromosome.
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