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Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin

Bivalent chromatin is characterized by occupation of both activating and repressive histone modifications. Here, we develop a mathematical model that involves antagonistic histone modifications H3K4me3 and H3K27me3 to capture the key features of bivalent chromatin. Three necessary conditions for the...

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Detalles Bibliográficos
Autores principales: Zhao, Wei, Qiao, Lingxia, Yan, Shiyu, Nie, Qing, Zhang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261666/
https://www.ncbi.nlm.nih.gov/pubmed/34278251
http://dx.doi.org/10.1016/j.isci.2021.102732
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author Zhao, Wei
Qiao, Lingxia
Yan, Shiyu
Nie, Qing
Zhang, Lei
author_facet Zhao, Wei
Qiao, Lingxia
Yan, Shiyu
Nie, Qing
Zhang, Lei
author_sort Zhao, Wei
collection PubMed
description Bivalent chromatin is characterized by occupation of both activating and repressive histone modifications. Here, we develop a mathematical model that involves antagonistic histone modifications H3K4me3 and H3K27me3 to capture the key features of bivalent chromatin. Three necessary conditions for the emergence of bivalent chromatin are identified, including advantageous methylating activity over demethylating activity, frequent noise conversions of modifications, and sufficient nonlinearity. The first condition is further confirmed by analyzing the existing experimental data. Investigation of the composition of bivalent chromatin reveals that bivalent nucleosomes carrying both H3K4me3 and H3K27me3 account for no more than half of nucleosomes at the bivalent chromatin domain. We identify that bivalent chromatin not only allows transitions to multiple states but also serves as a stepping stone to facilitate a stepwise transition between repressive chromatin state and activating chromatin state and thus elucidate crucial roles of bivalent chromatin in mediating phenotypical plasticity during cell fate determination.
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spelling pubmed-82616662021-07-16 Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin Zhao, Wei Qiao, Lingxia Yan, Shiyu Nie, Qing Zhang, Lei iScience Article Bivalent chromatin is characterized by occupation of both activating and repressive histone modifications. Here, we develop a mathematical model that involves antagonistic histone modifications H3K4me3 and H3K27me3 to capture the key features of bivalent chromatin. Three necessary conditions for the emergence of bivalent chromatin are identified, including advantageous methylating activity over demethylating activity, frequent noise conversions of modifications, and sufficient nonlinearity. The first condition is further confirmed by analyzing the existing experimental data. Investigation of the composition of bivalent chromatin reveals that bivalent nucleosomes carrying both H3K4me3 and H3K27me3 account for no more than half of nucleosomes at the bivalent chromatin domain. We identify that bivalent chromatin not only allows transitions to multiple states but also serves as a stepping stone to facilitate a stepwise transition between repressive chromatin state and activating chromatin state and thus elucidate crucial roles of bivalent chromatin in mediating phenotypical plasticity during cell fate determination. Elsevier 2021-06-17 /pmc/articles/PMC8261666/ /pubmed/34278251 http://dx.doi.org/10.1016/j.isci.2021.102732 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhao, Wei
Qiao, Lingxia
Yan, Shiyu
Nie, Qing
Zhang, Lei
Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
title Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
title_full Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
title_fullStr Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
title_full_unstemmed Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
title_short Mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
title_sort mathematical modeling of histone modifications reveals the formation mechanism and function of bivalent chromatin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261666/
https://www.ncbi.nlm.nih.gov/pubmed/34278251
http://dx.doi.org/10.1016/j.isci.2021.102732
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