Quantifying the Stability of Coupled Genetic and Epigenetic Switches With Variational Methods
Name
fgene-11-636724.pdf
Description
Published version
Size
3.04 MB
Format
Adobe PDF
Checksum (MD5)
b74dbab5f4fca4c92e2dd475c8dabdb0
Author(s)
Sood, Amogh
Zhang, Bin
Date Issued
2021
Journal
Frontiers in Genetics
Publisher
Frontiers Media SA
Version
Final published version
Abstract
The Waddington landscape provides an intuitive metaphor to view development as a ball rolling down the hill, with distinct phenotypes as basins and differentiation pathways as valleys. Since, at a molecular level, cell differentiation arises from interactions among the genes, a mathematical definition for the Waddington landscape can, in principle, be obtained by studying the gene regulatory networks. For eukaryotes, gene regulation is inextricably and intimately linked to histone modifications. However, the impact of such modifications on both landscape topography and stability of attractor states is not fully understood. In this work, we introduced a minimal kinetic model for gene regulation that combines the impact of both histone modifications and transcription factors. We further developed an approximation scheme based on variational principles to solve the corresponding master equation in a second quantized framework. By analyzing the steady-state solutions at various parameter regimes, we found that histone modification kinetics can significantly alter the behavior of a genetic network, resulting in qualitative changes in gene expression profiles. The emerging epigenetic landscape captures the delicate interplay between transcription factors and histone modifications in driving cell-fate decisions.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.3389/fgene.2020.636724
