1. T. Chen, M.A. Al-Radhawi, and E.D. Sontag. A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks. Epigenetics, 15:1-22, 2020. Note: PMID: 32842865. [PDF] [doi:10.1080/15592294.2020.1805686] Keyword(s): methylation, differentiation, epigenetics, pluripotent cells, gene regulatory networks, bistability, bistability, systems biology. Abstract:

   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, 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 methylation plays in enhancing the stability of the silenced gene state.

1. T. Chen, M. A. Al-Radhawi, and E. D. Sontag. A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks. Technical report, Cold Spring Harbor Laboratory, 2019. Note: BioRxiv preprint 10.1101/2019.12.19.883280. Keyword(s): Cell-fate networks, gene regulatory networks, DNA methylation, epigenetic regulation, pluripotent stem cell circuit. Abstract:

   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, 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 methylation plays in enhancing the stability of the silenced gene state.

This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders.

This document was translated from BibT_EX by bibtex2html