A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks
A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks
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DOI：
10.1080/15592294.2020.1805686
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发表时间：
2020-09-24
期刊：
影响因子：
3.7
通讯作者：
Sontag, Eduardo D.
中科院分区：
文献类型：
--
作者：
Chen, Tianchi;Al-Radhawi, M. Ali;Sontag, Eduardo D.
细胞命运网络传统上是在基因调控网络的框架内研究的。这种模式只考虑通过表达的转录因子的基因的相互作用，并不包括染色质修饰过程。本文介绍了一个数学模型，无缝结合基因调控网络和DNA甲基化（DNAm），定量表征表观遗传调控的基因沉默的贡献的目标。引入“吸引盆地百分比”作为量化基因沉默能力的度量。作为一个案例研究，进行了计算和理论分析的多能干细胞电路模型以及简化的自激活基因模型。结果证实，该方法定量捕获的关键作用，DNAm在提高沉默的基因状态的稳定性。
Cell-fate networks are traditionally studied within the framework of gene regulatory networks. This paradigm considers only interactions of genes through expressed transcription factors and does not incorporate chromatin modification processes. This paper introduces a mathematical model that seamlessly combines gene regulatory networks and DNA methylation (DNAm), with the goal of quantitatively characterizing the contribution of epigenetic regulation to gene silencing. The 'Basin of Attraction percentage' is introduced as a metric to quantify gene silencing abilities. As a case study, a computational and theoretical analysis is carried out for a model of the pluripotent stem cell circuit as well as a simplified self-activating gene model. The results confirm that the methodology quantitatively captures the key role that DNAm plays in enhancing the stability of the silenced gene state.