A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks
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 seamles...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-04-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2020.1805686 |
| _version_ | 1797678829843513344 |
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| author | Tianchi Chen M. Ali Al-Radhawi Eduardo D. Sontag |
| author_facet | Tianchi Chen M. Ali Al-Radhawi Eduardo D. Sontag |
| author_sort | Tianchi Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T23:05:40Z |
| format | Article |
| id | doaj.art-931b4a8f7e9042d495df2492cc3940f2 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:05:40Z |
| publishDate | 2021-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-931b4a8f7e9042d495df2492cc3940f22023-09-21T13:09:24ZengTaylor & Francis GroupEpigenetics1559-22941559-23082021-04-0116443645710.1080/15592294.2020.18056861805686A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networksTianchi Chen0M. Ali Al-Radhawi1Eduardo D. Sontag2Northeastern UniversityNortheastern UniversityNortheastern UniversityCell-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.http://dx.doi.org/10.1080/15592294.2020.1805686dna methylationstability boundarycell-fatetranscriptional regulationepigeneticsgene silencingbasin of attractionbistability |
| spellingShingle | Tianchi Chen M. Ali Al-Radhawi Eduardo D. Sontag A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks Epigenetics dna methylation stability boundary cell-fate transcriptional regulation epigenetics gene silencing basin of attraction bistability |
| title | A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks |
| title_full | A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks |
| title_fullStr | A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks |
| title_full_unstemmed | A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks |
| title_short | A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks |
| title_sort | mathematical model exhibiting the effect of dna methylation on the stability boundary in cell fate networks |
| topic | dna methylation stability boundary cell-fate transcriptional regulation epigenetics gene silencing basin of attraction bistability |
| url | http://dx.doi.org/10.1080/15592294.2020.1805686 |
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