Inheritance of epigenetic chromatin silencing

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

doi:https://doi.org/10.1016/j.jtbi.2008.12.021

Inheritance of epigenetic chromatin silencing

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

Rutgers, The State University

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	112-120
Number of pages	9
Journal	Journal of Theoretical Biology
Volume	258
Issue number	1
DOIs	https://doi.org/10.1016/j.jtbi.2008.12.021
State	Published - 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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title = "Inheritance of epigenetic chromatin silencing",

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.",

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note = "Funding Information: We acknowledge useful discussions with Adel Dayarian and Mohammad Sedighi. Two of the authors (A.M.S. and S.M.) were partially supported by an NHGRI Grant R01 HG03470-02. J.L.L.'s work was partially supported by NSF Grant DMR-0802120 and AFOSR Grant AF-FA-9550-04-4-22910.",

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N1 - Funding Information: We acknowledge useful discussions with Adel Dayarian and Mohammad Sedighi. Two of the authors (A.M.S. and S.M.) were partially supported by an NHGRI Grant R01 HG03470-02. J.L.L.'s work was partially supported by NSF Grant DMR-0802120 and AFOSR Grant AF-FA-9550-04-4-22910.

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N2 - 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.

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Inheritance of epigenetic chromatin silencing

Abstract

ASJC Scopus subject areas

Keywords

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