Information Integration and Energy Expenditure in Gene Regulation.
Information Integration and Energy Expenditure in Gene Regulation.
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DOI：
10.1016/j.cell.2016.06.012
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发表时间：
2016-06-30
期刊：
影响因子：
64.5
通讯作者：
Gunawardena J
中科院分区：
文献类型：
--
作者：
Estrada J;Wong F;DePace A;Gunawardena J
用于推理基因调控的定量概念在很大程度上源于细菌研究。我们发现这种细菌模式不能解释典型发育基因对调节转录因子（TF）的强烈表达。在没有能量消耗的情况下，当调控DNA处于热力学平衡时，跨多个TF结合位点的信息整合可以产生所需的清晰度，但对由此产生的“高阶协作性”有很强的约束。即使有了这样的整合，对于n个TF结合位点，仍然存在一个“霍普菲尔德屏障”，用希尔系数n的希尔函数表示。然而，如果能量被消耗来维持调控DNA远离热力学平衡，就像在动力学校对中一样，这个屏障可以被打破，从而获得更大的清晰度。我们的方法以基础物理学为基础，导致可测试的实验预测，并建议如何制定真核基因调控的定量范式。细菌基因调控的物理原理不能解释真核生物基因表达的尖锐性；能源使用和信息整合也必须考虑在内。
The quantitative concepts used to reason about gene regulation largely derive from bacterial studies. We show that this bacterial paradigm cannot explain the sharp expression of a canonical developmental gene in response to a regulating transcription factor (TF). In the absence of energy expenditure, with regulatory DNA at thermodynamic equilibrium, information integration across multiple TF binding sites can generate the required sharpness but with strong constraints on the resulting “higher-order cooperativities”. Even with such integration there is a “Hopfield barrier” to sharpness, represented, for n TF binding sites, by the Hill function with Hill coefficient n. If, however, energy is expended to maintain regulatory DNA away from thermodynamic equilibrium, as in kinetic proofreading, this barrier can be breached and greater sharpness achieved. Our approach is grounded in fundamental physics, leads to testable experimental predictions and suggests how a quantitative paradigm for eukaryotic gene regulation can be formulated. The physical principles governing gene regulation in bacteria can't explain the sharpness of gene expression in eukaryotes; energy use and information integration have to be taken into account as well.