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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66454 |
| _version_ | 1811181422614937600 |
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| author | Cecilia Lövkvist Pawel Mikulski Svenja Reeck Matthew Hartley Caroline Dean Martin Howard |
| author_facet | Cecilia Lövkvist Pawel Mikulski Svenja Reeck Matthew Hartley Caroline Dean Martin Howard |
| author_sort | Cecilia Lövkvist |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T09:17:32Z |
| format | Article |
| id | doaj.art-deb1dee8e54f4eeaa8d0b9c835f69586 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:17:32Z |
| publishDate | 2021-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-deb1dee8e54f4eeaa8d0b9c835f695862022-12-22T04:32:18ZengeLife Sciences Publications LtdeLife2050-084X2021-09-011010.7554/eLife.66454Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memoryCecilia Lövkvist0https://orcid.org/0000-0001-7696-7814Pawel Mikulski1Svenja Reeck2Matthew Hartley3Caroline Dean4https://orcid.org/0000-0002-6555-3525Martin Howard5https://orcid.org/0000-0001-7670-0781Computational and Systems Biology, John Innes Centre, Norwich Research Park, United KingdomCell and Developmental Biology, John Innes Centre, Norwich Research Park, United KingdomComputational and Systems Biology, John Innes Centre, Norwich Research Park, United Kingdom; Cell and Developmental Biology, John Innes Centre, Norwich Research Park, United KingdomComputational and Systems Biology, John Innes Centre, Norwich Research Park, United KingdomCell and Developmental Biology, John Innes Centre, Norwich Research Park, United KingdomComputational and Systems Biology, John Innes Centre, Norwich Research Park, United KingdomThe 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.https://elifesciences.org/articles/66454FLCepigeneticsmathematical modellingPRC2polycombH3K27me3 |
| spellingShingle | Cecilia Lövkvist Pawel Mikulski Svenja Reeck Matthew Hartley Caroline Dean Martin Howard Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory eLife FLC epigenetics mathematical modelling PRC2 polycomb H3K27me3 |
| 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 | FLC epigenetics mathematical modelling PRC2 polycomb H3K27me3 |
| url | https://elifesciences.org/articles/66454 |
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