Dynamical modeling of the H3K27 epigenetic landscape in mouse embryonic stem cells - Archive ouverte HAL
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Pré-publication, Document de travail

Dynamical modeling of the H3K27 epigenetic landscape in mouse embryonic stem cells

Kapil Newar 1 Eric Fanchon 1 Daniel Jost 2
1 TIMC-BCM - Biologie Computationnelle et Modélisation
TIMC - Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525
Abstract : Abstract The Polycomb system via the methylation of the lysine 27 of histone H3 (H3K27) plays central roles in the silencing of many lineage-specific genes during development. Recent experimental evidence suggested that the recruitment of histone modifying enzymes like the Polycomb repressive complex 2 (PRC2) at specific sites and their spreading capacities from these sites are key to the establishment and maintenance of a proper epigenomic landscape around Polycomb-target genes. Here, based on previous biochemical knowledge, we turned this hypothesis into a mathematical model that can predict the locus-specific distributions of H3K27 modifications. Within the biological context of mouse embryonic stem cells, our model showed quantitative agreement with experimental profiles of H3K27 acetylation and methylation around Polycomb-target genes in wild-type and mutants. In particular, we demonstrated the key role of the reader-writer module of PRC2 and of the competition between the binding of activating and repressing enzymes in shaping the H3K27 landscape around transcriptional start sites. The predicted dynamics of establishment and maintenance of the repressive trimethylated H3K27 state suggest a slow accumulation, in perfect agreement with experiments. Our approach represents a first step towards a quantitative description of PcG regulation in various cellular contexts and provides a generic framework to better characterize epigenetic regulation in normal or disease situations.
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Pré-publication, Document de travail
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https://hal.archives-ouvertes.fr/hal-03431877
Contributeur : Daniel Jost Connectez-vous pour contacter le contributeur
Soumis le : mardi 16 novembre 2021 - 23:39:07
Dernière modification le : jeudi 27 janvier 2022 - 16:28:43
Archivage à long terme le : : jeudi 17 février 2022 - 21:34:26

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Kapil Newar, Eric Fanchon, Daniel Jost. Dynamical modeling of the H3K27 epigenetic landscape in mouse embryonic stem cells. 2021. ⟨hal-03431877⟩

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