A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks

Tianchi Chen, M. Ali Al-Radhawi, Eduardo D. Sontag

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 (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.

Original languageEnglish (US)
Pages (from-to)436-457
Number of pages22
JournalEpigenetics
Volume16
Issue number4
DOIs
StatePublished - 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Keywords

  • DNA methylation
  • basin of attraction
  • bistability
  • cell-fate
  • epigenetics
  • gene silencing
  • stability boundary
  • transcriptional regulation

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