基因表达谱中两种不同的逻辑网络控制类型
Two distinct logical types of network control in gene expression profiles
摘要:
在细菌等单细胞生物中,在一种环境中有益的相同获得性突变在另一种环境中可能是限制性的。然而,不断发展的大肠杆菌种群在适应方面表现出显着的灵活性。维持遗传灵活性的机制仍不清楚。在大肠在大肠杆菌中,基因表达的转录调控既涉及以高亲和力结合特定DNA位点的专用调节因子,也涉及全局调节因子-细菌类色体的丰富DNA结构蛋白结合多个低亲和力位点,从而调节DNA的超螺旋密度。第一种形式的转录调控主要是成对的和特定的,代表数字控制,而第二种形式是(在强度和分布)连续的,代表模拟控制。在这里,我们看看来自显着的基因表达变化的两种形式的控制下的有效网络的属性,并发现在一种类型的控制(例如,由突变引起的全局DNA结构因子)的限制,另一种类型可以补偿受损的调节。全球监管机构的突变显着增强数字控制;在全球DNA架构蛋白质的存在下,监管主要是模拟类型,耦合空间相邻的基因组位点;我们的数据表明,两种逻辑上不同类型的控制相互平衡。通过揭示两种不同的逻辑类型的控制,我们的方法提供了基本的见解转录调控的组织原则和缓冲遗传灵活性的机制。我们预计,区分逻辑控制类型的一般概念将适用于许多复杂的生物网络。
英文摘要:
In unicellular organisms such as bacteria the same acquired mutations beneficial in one environment can be restrictive in another. However, evolving Escherichia coli populations demonstrate remarkable flexibility in adaptation. The mechanisms sustaining genetic flexibility remain unclear. In E. coli the transcriptional regulation of gene expression involves both dedicated regulators binding specific DNA sites with high affinity and also global regulators - abundant DNA architectural proteins of the bacterial chromoid binding multiple low affinity sites and thus modulating the superhelical density of DNA. The first form of transcriptional regulation is dominantly pairwise and specific, representing digitial control, while the second form is (in strength and distribution) continuous, representing analog control. Here we look at the properties of effective networks derived from significant gene expression changes under variation of the two forms of control and find that upon limitations of one type of control (caused e.g. by mutation of a global DNA architectural factor) the other type can compensate for compromised regulation. Mutations of global regulators significantly enhance the digital control; in the presence of global DNA architectural proteins regulation is mostly of the analog type, coupling spatially neighboring genomic loci; together our data suggest that two logically distinct types of control are balancing each other. By revealing two distinct logical types of control, our approach provides basic insights into both the organizational principles of transcriptional regulation and the mechanisms buffering genetic flexibility. We anticipate that the general concept of distinguishing logical types of control will apply to many complex biological networks.
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