Computational Modeling to Elucidate Molecular Mechanisms of Epigenetic Memory

Abstract

(100-250 words)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 Book chapter in Epigenetic Technological Applications (Elsevier), in press 2 covalent modification inheritance. We will pedagogically introduce the typical procedure and some technical details of performing a mathematical modeling study, and discuss future developments. Keywords (5-10)Histone epigenetic memory, mathematical modeling, reader and writer, pattern reconstruction, stochastic dynamics, histone modification enzyme, post-translational modification Outline:In this chapter we discuss how to use mathematical modeling to explore the dynamics and mechanism of histone modification dynamics. Book chapter inEpigenetic Technological Applications (Elsevier), in press 3 Textbody