Theory for stability and regulation of epigenetic landscapes

TL;DR

This paper develops a theoretical framework using a transfer matrix method to analyze the stability and regulation of epigenetic landscapes, focusing on bistability and heritable phenotypic states during cell division.

Contribution

It introduces a rigorous, generalized model for epigenetic bistability, incorporating noise and cell division effects, advancing understanding of heritable cellular states.

Findings

Provides a method to calculate stability of epigenetic states

Models the impact of noise and cell division on epigenetic landscapes

Offers insights into the regulation of heritable phenotypes

Abstract

Cells can often choose among several stably heritable phenotypes. Examples are the expression of genes in eukaryotic cells where long chromosomal regions can adopt persistent and heritable silenced or active states, that may be associated with positive feedback in dynamic modification of nucleosomes. We generalize this mechanism in terms of bistability associated with valleys in an epigenetic landscape. A transfer matrix method was used to rigorously follow the system through the disruptive process of cell division. This combined treatment of noisy dynamics both between and during cell division provides an efficient way to calculate the stability of alternative states in a broad range of epigenetic systems.