Modeling the Dynamic Epigenome: From Histone Modifications Towards Self-Organizing Chromatin

Abstract

Epigenetic mechanisms play an important role in regulating and stabilizing functional states of living cells. However, in spite of an increasing amount of experimental data, models of transcriptional regulation by epigenetic processes, in particular by histone modifications, are rather rare. In this article, we focus on epigenetic modes of transcriptional regulation based on histone modifications and their potential dynamical interplay with DNA methylation and higher-order chromatin structure. The main purpose of this article is to review recent formal modeling approaches to the dynamics and propagation of histone modifications and to relate them to available experimental data. We evaluate their assumptions with respect to recruitment of relevant modifiers, establishment and processing of modifications, and compare the emerging stability properties and memory effects. Theoretical predictions that await experimental validation are highlighted and potential extensions of these models towards multiscale models of self-organizing chromatin are discussed.

KEYWORDS::

• bistability
• chromatin remodeling
• cooperative binding
• epigenetic memory
• heritable cell fates
• histone modification
• multistate conversion
• theoretical model
• transcriptional regulation

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.