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[基因表达调控过程中的统计涨落:从统计力学角度对该问题的思考]

[Statistical fluctuations in processes of gene expression regulation: consideration of the problem from point of view of statistical mechanics].

作者信息

Nechipurenko Iu D, Wolf A M, Gurskiĭ G V

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Physical Department, Lomonosov Moscow State University, Bioanaliticheskie Tekhnologii Company, Moscow, Russia.

出版信息

Biofizika. 2003 Nov-Dec;48(6):986-97.

PMID:14714515
Abstract

The regulation of gene expression is a basic problem of biology. In some cases, the gene activity is regulated by specific binding of regulatory proteins to DNA. In terms of statistical mechanics, this binding is described as the process of adsorption of ligands on the one-dimensional lattice and has a probability nature. As a random physical process, the adsorption of regulatory proteins on DNA introduces a noise to the regulation of gene activity. We derived equations, which make it possible to estimate this noise in the case of the binding of the lac repressor to the operator and showed that these estimates correspond to experimental data. Many ligands are able to bind nonspecifically to DNA. Nonspecific binding is characterized by a lesser equilibrium constant but a greater number of binding sites on the DNA, as compared with specific binding. Relations are presented, which enable one to estimate the probability of the binding of a ligand on a specific site and on nonspecific sites on DNA. The competition between specific and nonspecific binding of regulatory proteins plays a great role in the regulation of gene activity. Similar to the one-dimensional "lattice gas" of particles, ligands adsorbed on DNA produce "one-dimensional" pressure on proteins located at the termini of free regions of DNA. This pressure, an analog of osmotic pressure, may be of importance in processes leading to changes in chromatin structure and activation of gene expression.

摘要

基因表达的调控是生物学的一个基本问题。在某些情况下,基因活性是通过调节蛋白与DNA的特异性结合来调控的。从统计力学的角度来看,这种结合被描述为配体在一维晶格上的吸附过程,具有概率性质。作为一个随机物理过程,调节蛋白在DNA上的吸附给基因活性的调控引入了噪声。我们推导了一些方程,这些方程使得在乳糖阻遏物与操纵基因结合的情况下能够估计这种噪声,并表明这些估计与实验数据相符。许多配体能够非特异性地与DNA结合。与特异性结合相比,非特异性结合的特征是平衡常数较小,但DNA上的结合位点较多。文中给出了一些关系式,这些关系式能够让人估计配体在DNA上特异性位点和非特异性位点结合的概率。调节蛋白特异性和非特异性结合之间的竞争在基因活性调控中起着重要作用。与粒子的一维“晶格气体”类似,吸附在DNA上的配体对位于DNA自由区域末端的蛋白质产生“一维”压力。这种压力类似于渗透压,在导致染色质结构变化和基因表达激活的过程中可能很重要。

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