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Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory
The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replica...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412945/ https://www.ncbi.nlm.nih.gov/pubmed/34473050 http://dx.doi.org/10.7554/eLife.66454 |
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author | Lövkvist, Cecilia Mikulski, Pawel Reeck, Svenja Hartley, Matthew Dean, Caroline Howard, Martin |
author_facet | Lövkvist, Cecilia Mikulski, Pawel Reeck, Svenja Hartley, Matthew Dean, Caroline Howard, Martin |
author_sort | Lövkvist, Cecilia |
collection | PubMed |
description | The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replication. However, for some PRC2 targets, a purely histone-based system for epigenetic inheritance may be insufficient. We address this issue at the Polycomb target FLOWERING LOCUS C (FLC) in Arabidopsis thaliana, as a narrow nucleation region of only ~three nucleosomes within FLC mediates epigenetic state switching and subsequent memory over many cell cycles. To explain the memory’s unexpected persistence, we introduce a mathematical model incorporating extra protein memory storage elements with positive feedback that persist at the locus through DNA replication, in addition to histone modifications. Our hybrid model explains many features of epigenetic switching/memory at FLC and encapsulates generic mechanisms that may be widely applicable. |
format | Online Article Text |
id | pubmed-8412945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-84129452021-09-10 Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory Lövkvist, Cecilia Mikulski, Pawel Reeck, Svenja Hartley, Matthew Dean, Caroline Howard, Martin eLife Physics of Living Systems The histone modification H3K27me3 plays a central role in Polycomb-mediated epigenetic silencing. H3K27me3 recruits and allosterically activates Polycomb Repressive Complex 2 (PRC2), which adds this modification to nearby histones, providing a read/write mechanism for inheritance through DNA replication. However, for some PRC2 targets, a purely histone-based system for epigenetic inheritance may be insufficient. We address this issue at the Polycomb target FLOWERING LOCUS C (FLC) in Arabidopsis thaliana, as a narrow nucleation region of only ~three nucleosomes within FLC mediates epigenetic state switching and subsequent memory over many cell cycles. To explain the memory’s unexpected persistence, we introduce a mathematical model incorporating extra protein memory storage elements with positive feedback that persist at the locus through DNA replication, in addition to histone modifications. Our hybrid model explains many features of epigenetic switching/memory at FLC and encapsulates generic mechanisms that may be widely applicable. eLife Sciences Publications, Ltd 2021-09-02 /pmc/articles/PMC8412945/ /pubmed/34473050 http://dx.doi.org/10.7554/eLife.66454 Text en © 2021, Lövkvist et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Physics of Living Systems Lövkvist, Cecilia Mikulski, Pawel Reeck, Svenja Hartley, Matthew Dean, Caroline Howard, Martin Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory |
title | Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory |
title_full | Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory |
title_fullStr | Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory |
title_full_unstemmed | Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory |
title_short | Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory |
title_sort | hybrid protein assembly-histone modification mechanism for prc2-based epigenetic switching and memory |
topic | Physics of Living Systems |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412945/ https://www.ncbi.nlm.nih.gov/pubmed/34473050 http://dx.doi.org/10.7554/eLife.66454 |
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