On the thermodynamics of DNA methylation process.
On the thermodynamics of DNA methylation process.
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DOI：
10.1038/s41598-023-35166-9
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发表时间：
2023-06-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA甲基化是一种表观遗传机制，在转录和转录后调控、基因组印迹、衰老以及对环境变化和疾病的应激反应等多种生物过程中发挥重要作用。根据生命系统中的热力学原理和最大熵原理的应用，我们提出了一个理解和解码DNA甲基化过程的理论框架。这一论点的核心原则是，DNA甲基化信息发散的概率密度函数总结了自发甲基化背景下的统计生物物理学，并隐含地与符合香农容量定理的分子机器的通道容量有关。在这个理论基础上，分子机器（酶）逻辑运算对吉布熵(S)和亥姆霍兹自由能(F)的贡献是内在的。对拟南芥数据集S的估计表明，作为一个热力学状态变量，个体甲基组熵完全由系统的当前状态决定，从生物学角度来说，这意味着估计的熵值与可观察到的表型状态之间的对应关系。在不同类型的癌症患者中，研究结果表明，从分化（健康）组织到癌细胞的转变过程中发生了显著的信息丢失。这种类型的分析可能对早期诊断有重要意义。对实验数据集的熵波动的分析表明，生物体对环境变化的反应引起的全基因组甲基化变化的幅度存在限制。只有在拟南芥突变体met1和癌细胞中观察到的功能失调阶段不符合这些规则。
DNA methylation is an epigenetic mechanism that plays important roles in various biological processes including transcriptional and post-transcriptional regulation, genomic imprinting, aging, and stress response to environmental changes and disease. Consistent with thermodynamic principles acting within living systems and the application of maximum entropy principle, we propose a theoretical framework to understand and decode the DNA methylation process. A central tenet of this argument is that the probability density function of DNA methylation information-divergence summarizes the statistical biophysics underlying spontaneous methylation background and implicitly bears on the channel capacity of molecular machines conforming to Shannon’s capacity theorem. On this theoretical basis, contributions from the molecular machine (enzyme) logical operations to Gibb entropy (S) and Helmholtz free energy (F) are intrinsic. Application to the estimations of S on datasets from Arabidopsis thaliana suggests that, as a thermodynamic state variable, individual methylome entropy is completely determined by the current state of the system, which in biological terms translates to a correspondence between estimated entropy values and observable phenotypic state. In patients with different types of cancer, results suggest that a significant information loss occurs in the transition from differentiated (healthy) tissues to cancer cells. This type of analysis may have important implications for early-stage diagnostics. The analysis of entropy fluctuations on experimental datasets revealed existence of restrictions on the magnitude of genome-wide methylation changes originating by organismal response to environmental changes. Only dysfunctional stages observed in the Arabidopsis mutant met1 and in cancer cells do not conform to these rules.
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影响因子：
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