Computational modeling to elucidate molecular mechanisms of epigenetic memory

TL;DR

This paper reviews how computational models help understand the molecular mechanisms behind epigenetic memory and cell phenotype inheritance, highlighting recent advances and future directions in the field.

Contribution

It provides a pedagogical overview of mathematical modeling approaches used to elucidate epigenetic inheritance mechanisms in developmental biology.

Findings

Mathematical models clarify DNA methylation inheritance.

Models reveal histone modification dynamics.

Future modeling directions are discussed.

Abstract

How do mammalian cells that share the same genome exist in notably distinct phenotypes, exhibiting differences in morphology, gene expression patterns, and epigenetic chromatin statuses? Furthermore how do cells of different phenotypes differentiate reproducibly from a single fertilized egg? These are fundamental problems in developmental biology. Epigenetic histone modifications play an important role in the maintenance of different cell phenotypes. The exact molecular mechanism for inheritance of the modification patterns over cell generations remains elusive. The complexity comes partly from the number of molecular species and the broad time scales involved. In recent years mathematical modeling has made significant contributions on elucidating the molecular mechanisms of DNA methylation and histone covalent modification inheritance. We will pedagogically introduce the typical procedure and some technical details of performing a mathematical modeling study, and discuss future developments.