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Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains

BACKGROUND: Localized functional domains within chromosomes, known as topologically associating domains (TADs), have been recently highlighted. In Drosophila, TADs are biochemically defined by epigenetic marks, this suggesting that the 3D arrangement may be the “missing link” between epigenetics and...

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Autores principales: Lesage, Antony, Dahirel, Vincent, Victor, Jean-Marc, Barbi, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515630/
https://www.ncbi.nlm.nih.gov/pubmed/31084607
http://dx.doi.org/10.1186/s13072-019-0269-6
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author Lesage, Antony
Dahirel, Vincent
Victor, Jean-Marc
Barbi, Maria
author_facet Lesage, Antony
Dahirel, Vincent
Victor, Jean-Marc
Barbi, Maria
author_sort Lesage, Antony
collection PubMed
description BACKGROUND: Localized functional domains within chromosomes, known as topologically associating domains (TADs), have been recently highlighted. In Drosophila, TADs are biochemically defined by epigenetic marks, this suggesting that the 3D arrangement may be the “missing link” between epigenetics and gene activity. Recent observations (Boettiger et al. in Nature 529(7586):418–422, 2016) provide access to structural features of these domains with unprecedented resolution thanks to super-resolution experiments. In particular, they give access to the distribution of the radii of gyration for domains of different linear length and associated with different transcriptional activity states: active, inactive or repressed. Intriguingly, the observed scaling laws lack consistent interpretation in polymer physics. RESULTS: We develop a new methodology conceived to extract the best information from such super-resolution data by exploiting the whole distribution of gyration radii, and to place these experimental results on a theoretical framework. We show that the experimental data are compatible with the finite-size behavior of a self-attracting polymer. The same generic polymer model leads to quantitative differences between active, inactive and repressed domains. Active domains behave as pure polymer coils, while inactive and repressed domains both lie at the coil–globule crossover. For the first time, the “color-specificity” of both the persistence length and the mean interaction energy are estimated, leading to important differences between epigenetic states. CONCLUSION: These results point toward a crucial role of criticality to enhance the system responsivity, resulting in both energy transitions and structural rearrangements. We get strong indications that epigenetically induced changes in nucleosome–nucleosome interaction can cause chromatin to shift between different activity states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13072-019-0269-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-65156302019-05-21 Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains Lesage, Antony Dahirel, Vincent Victor, Jean-Marc Barbi, Maria Epigenetics Chromatin Research BACKGROUND: Localized functional domains within chromosomes, known as topologically associating domains (TADs), have been recently highlighted. In Drosophila, TADs are biochemically defined by epigenetic marks, this suggesting that the 3D arrangement may be the “missing link” between epigenetics and gene activity. Recent observations (Boettiger et al. in Nature 529(7586):418–422, 2016) provide access to structural features of these domains with unprecedented resolution thanks to super-resolution experiments. In particular, they give access to the distribution of the radii of gyration for domains of different linear length and associated with different transcriptional activity states: active, inactive or repressed. Intriguingly, the observed scaling laws lack consistent interpretation in polymer physics. RESULTS: We develop a new methodology conceived to extract the best information from such super-resolution data by exploiting the whole distribution of gyration radii, and to place these experimental results on a theoretical framework. We show that the experimental data are compatible with the finite-size behavior of a self-attracting polymer. The same generic polymer model leads to quantitative differences between active, inactive and repressed domains. Active domains behave as pure polymer coils, while inactive and repressed domains both lie at the coil–globule crossover. For the first time, the “color-specificity” of both the persistence length and the mean interaction energy are estimated, leading to important differences between epigenetic states. CONCLUSION: These results point toward a crucial role of criticality to enhance the system responsivity, resulting in both energy transitions and structural rearrangements. We get strong indications that epigenetically induced changes in nucleosome–nucleosome interaction can cause chromatin to shift between different activity states. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13072-019-0269-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-13 /pmc/articles/PMC6515630/ /pubmed/31084607 http://dx.doi.org/10.1186/s13072-019-0269-6 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Lesage, Antony
Dahirel, Vincent
Victor, Jean-Marc
Barbi, Maria
Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains
title Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains
title_full Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains
title_fullStr Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains
title_full_unstemmed Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains
title_short Polymer coil–globule phase transition is a universal folding principle of Drosophila epigenetic domains
title_sort polymer coil–globule phase transition is a universal folding principle of drosophila epigenetic domains
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515630/
https://www.ncbi.nlm.nih.gov/pubmed/31084607
http://dx.doi.org/10.1186/s13072-019-0269-6
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