The histone chaperone FACT facilitates heterochromatin spreading through regulation of histone turnover and H3K9 methylation states

Murawska, Magdalena; Greenstein, R A; Schauer, Tamás; Olsen, Karl C.F.; Ng, Henry; Ladurner, Andreas G.; Al-Sady, Bassem; Braun, Sigurd

doi:10.1101/2021.06.30.450523

Cited by 2 publications

(2 citation statements)

References 67 publications

(92 reference statements)

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“…In particular, it would be interesting to investigate the generality of the inferred parameters for more differentiated cells where H3K27me3 domains are usually more extended around PcG-target genes than in mESCs. It would allow to understand if these changes are solely due to differential HME binding, to modifications of rates like histone turnover [ 76 , 90 ] or to some unconsidered mechanisms as discussed above. More generally, our approach represents a first step towards a quantitative description of PcG regulation in various cellular contexts where ‘secondary’ effects may be integrated step-by-step to better estimate their importance in normal or disease contexts.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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, to test whether such mechanisms, as a minimal set of qualitative rules, are quantitatively compatible with data, we developed a mathematical model that can predict the locus-specific distributions of H3K27 modifications based on previous biochemical knowledge. 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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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In particular, it would be interesting to investigate the generality of the inferred parameters for more differentiated cells where H3K27me3 domains are usually more extended around PcG-target genes than in mESCs. It would allow to understand if these changes are solely due to differential HME binding, to modifications of rates like histone turnover (73,86) or to some unconsidered mechanisms as discussed above. More generally, our approach represents a first step towards a quantitative description of PcG regulation in various cellular contexts where 'secondary' effects may be integrated step-by-step to better estimate their importance in normal or disease contexts.…”

Section: Discussionmentioning

confidence: 99%

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

Newar

Fanchon

Jost³

2021

Preprint

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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.

show abstract

The histone chaperone FACT facilitates heterochromatin spreading through regulation of histone turnover and H3K9 methylation states

Cited by 2 publications

References 67 publications

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

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

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

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