Inheritance of epigenetic chromatin silencing

Diana David-Rus, Swagatam Mukhopadhyay, Joel L. Lebowitz, Anirvan M. Sengupta

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Maintenance of alternative chromatin states through cell divisions pose some fundamental constraints on the dynamics of histone modifications. In this paper, we study the systems biology of epigenetic inheritance by defining and analyzing general classes of mathematical models. We discuss how the number of modification states involved plays an essential role in the stability of epigenetic states. In addition, DNA duplication and the consequent dilution of marked histones act as a large perturbation for a stable state of histone modifications. The requirement that this large perturbation falls into the basin of attraction of the original state sometimes leads to additional constraints on effective models. Two such models, inspired by two different biological systems, are compared in their fulfilling the requirements of multistability and of recovery after DNA duplication. We conclude that in the presence of multiple histone modifications that characterize alternative epigenetic stable states, these requirements are more easily fulfilled.

Original languageEnglish (US)
Pages (from-to)112-120
Number of pages9
JournalJournal of Theoretical Biology
Volume258
Issue number1
DOIs
StatePublished - May 7 2009

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Keywords

  • Bistability
  • Cell cycle
  • Epigenetics
  • Histone modification
  • Silencing

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