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Boundaries potentiate polycomb response element-mediated silencing
BACKGROUND: Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170967/ https://www.ncbi.nlm.nih.gov/pubmed/34078365 http://dx.doi.org/10.1186/s12915-021-01047-8 |
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author | Erokhin, Maksim Gorbenko, Fedor Lomaev, Dmitry Mazina, Marina Yu Mikhailova, Anna Garaev, Azat K. Parshikov, Aleksander Vorobyeva, Nadezhda E. Georgiev, Pavel Schedl, Paul Chetverina, Darya |
author_facet | Erokhin, Maksim Gorbenko, Fedor Lomaev, Dmitry Mazina, Marina Yu Mikhailova, Anna Garaev, Azat K. Parshikov, Aleksander Vorobyeva, Nadezhda E. Georgiev, Pavel Schedl, Paul Chetverina, Darya |
author_sort | Erokhin, Maksim |
collection | PubMed |
description | BACKGROUND: Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements termed polycomb response elements (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside of their normal context, often by pairing sensitive (PSS) mechanism; however, their silencing activity is non-autonomous and depends upon the surrounding chromatin context. It is not known why PRE activity depends on the local environment or what outside factors can induce silencing. RESULTS: Using an attP system in Drosophila, we find that the so-called neutral chromatin environments vary substantially in their ability to support the silencing activity of the well-characterized bxdPRE. In refractory chromosomal contexts, factors required for PcG-silencing are unable to gain access to the PRE. Silencing activity can be rescued by linking the bxdPRE to a boundary element (insulator). When placed next to the PRE, the boundaries induce an alteration in chromatin structure enabling factors critical for PcG silencing to gain access to the bxdPRE. When placed at a distance from the bxdPRE, boundaries induce PSS by bringing the bxdPREs on each homolog in close proximity. CONCLUSION: This proof-of-concept study demonstrates that the repressing activity of PREs can be induced or enhanced by nearby boundary elements. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01047-8. |
format | Online Article Text |
id | pubmed-8170967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81709672021-06-03 Boundaries potentiate polycomb response element-mediated silencing Erokhin, Maksim Gorbenko, Fedor Lomaev, Dmitry Mazina, Marina Yu Mikhailova, Anna Garaev, Azat K. Parshikov, Aleksander Vorobyeva, Nadezhda E. Georgiev, Pavel Schedl, Paul Chetverina, Darya BMC Biol Research Article BACKGROUND: Epigenetic memory plays a critical role in the establishment and maintenance of cell identities in multicellular organisms. Polycomb and trithorax group (PcG and TrxG) proteins are responsible for epigenetic memory, and in flies, they are recruited to specialized DNA regulatory elements termed polycomb response elements (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside of their normal context, often by pairing sensitive (PSS) mechanism; however, their silencing activity is non-autonomous and depends upon the surrounding chromatin context. It is not known why PRE activity depends on the local environment or what outside factors can induce silencing. RESULTS: Using an attP system in Drosophila, we find that the so-called neutral chromatin environments vary substantially in their ability to support the silencing activity of the well-characterized bxdPRE. In refractory chromosomal contexts, factors required for PcG-silencing are unable to gain access to the PRE. Silencing activity can be rescued by linking the bxdPRE to a boundary element (insulator). When placed next to the PRE, the boundaries induce an alteration in chromatin structure enabling factors critical for PcG silencing to gain access to the bxdPRE. When placed at a distance from the bxdPRE, boundaries induce PSS by bringing the bxdPREs on each homolog in close proximity. CONCLUSION: This proof-of-concept study demonstrates that the repressing activity of PREs can be induced or enhanced by nearby boundary elements. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01047-8. BioMed Central 2021-06-02 /pmc/articles/PMC8170967/ /pubmed/34078365 http://dx.doi.org/10.1186/s12915-021-01047-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Erokhin, Maksim Gorbenko, Fedor Lomaev, Dmitry Mazina, Marina Yu Mikhailova, Anna Garaev, Azat K. Parshikov, Aleksander Vorobyeva, Nadezhda E. Georgiev, Pavel Schedl, Paul Chetverina, Darya Boundaries potentiate polycomb response element-mediated silencing |
title | Boundaries potentiate polycomb response element-mediated silencing |
title_full | Boundaries potentiate polycomb response element-mediated silencing |
title_fullStr | Boundaries potentiate polycomb response element-mediated silencing |
title_full_unstemmed | Boundaries potentiate polycomb response element-mediated silencing |
title_short | Boundaries potentiate polycomb response element-mediated silencing |
title_sort | boundaries potentiate polycomb response element-mediated silencing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170967/ https://www.ncbi.nlm.nih.gov/pubmed/34078365 http://dx.doi.org/10.1186/s12915-021-01047-8 |
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