Control of DNA structure and gene expression.
Control of DNA structure and gene expression.
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DNA 结构和基因表达的控制。
DOI：
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
M. V. van Workum
中科院分区：
文献类型：
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作者：
H. Westerhoff;M. V. van Workum
在通常的代谢控制理论中，酶的浓度被认为是参数而不是变量，即，当系统松弛到新的稳定状态时，它们保持恒定。它们只能通过干预措施重新设定。这种类型的控制分析对于理解代谢控制的原理以及理解太快或在太有限的代谢系统中涉及基因表达变化的代谢变化很有用。在实际的生命系统中，代谢变化往往伴随着基因表达的变化。在这方面的贡献，我们将说明如何代谢控制分析是丰富的基因表达是可变的。为了讨论可变基因表达控制分析中出现的新原理，我们将首先讨论理论模型系统。在第一种情况下，基因的数量是固定的，但mRNA和酶的浓度由RNA聚合酶、RNA酶、核糖体和蛋白酶的活性决定。第二，在翻译水平上存在代谢物的反馈抑制。将定义量化调节环强度的新系数。还系数，表明在何种程度上这些监管力度本身是由系统参数控制，定义并提供了一个求和定理。我们采用的实验模型系统，解决了在原核生物中，转录速率受DNA超螺旋程度影响的现象。这包括编码参与DNA超螺旋调节的两种酶（DNA促旋酶和拓扑异构酶I）的基因的转录。在离体条件下，ATP的水解自由能影响DNA促旋酶的活性。我们将提出细胞自由能状态影响DNA超螺旋的实验证据。我们还将讨论检查活性转录对活性DNA超螺旋的影响的实验。此外，该系统将在控制分析与可变基因表达方面进行分析;在这里，四个层次水平（DNA，RNA，酶，代谢物）相互作用，增加了控制分析的复杂性。
In the usual metabolic control theory, the concentrations of enzymes are considered to be parameters rather than variables, i.e., they remain constant as the system relaxes to a new steady state. They can only be reset by interventions. This type of control analysis is useful for understanding principles of metabolic control, and for understanding metabolic changes that are too quick or in too limited a metabolic system to involve changes in gene expression. In actual living systems, metabolic changes are often accompanied by changes in gene expression. In this contribution we shall illustrate how metabolic control analysis is enriched when gene expression is variable. To discuss the new principles emerging in control analysis with variable gene expression, we shall first discuss theoretical model systems. In the first, the number of genes is fixed, but the concentrations of mRNA and enzymes are determined by the activities of RNA polymerase, RNAases, ribosomes and proteases. In a second, there is feedback repression by a metabolite at the level of translation. New coefficients quantifying the strength of regulatory loops will be defined. Also coefficients that indicate to what extent these regulatory strengths themselves are controlled by system parameters, are defined and provided with a summation theorem. The experimental model system we employ, addresses the phenomenon that in prokaryotes, transcription rates are influenced by the extent of supercoiling of the DNA. This includes the transcription of the genes encoding the two enzymes (DNA gyrase and topoisomerase I) involved in the regulation of DNA supercoiling. In vitro the activity of DNA gyrase is influenced by the hydrolytic free energy of ATP. We shall present experimental evidence that the cellular free-energy state influences DNA supercoiling. We shall also discuss experiments inspecting the effect of active transcription on active DNA supercoiling. Also this system will be analyzed in terms of the control analysis with variable gene expression; here the four hierarchical levels (DNA, RNA, enzymes, metabolites) interact, adding complexity to the control analysis.