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TADs are 3D structural units of higher-order chromosome organization in Drosophila
Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains define...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829972/ https://www.ncbi.nlm.nih.gov/pubmed/29503869 http://dx.doi.org/10.1126/sciadv.aar8082 |
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author | Szabo, Quentin Jost, Daniel Chang, Jia-Ming Cattoni, Diego I. Papadopoulos, Giorgio L. Bonev, Boyan Sexton, Tom Gurgo, Julian Jacquier, Caroline Nollmann, Marcelo Bantignies, Frédéric Cavalli, Giacomo |
author_facet | Szabo, Quentin Jost, Daniel Chang, Jia-Ming Cattoni, Diego I. Papadopoulos, Giorgio L. Bonev, Boyan Sexton, Tom Gurgo, Julian Jacquier, Caroline Nollmann, Marcelo Bantignies, Frédéric Cavalli, Giacomo |
author_sort | Szabo, Quentin |
collection | PubMed |
description | Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear. Using a combination of Hi-C, three-dimensional (3D) fluorescent in situ hybridization, super-resolution microscopy, and polymer modeling, we provide an integrative view of chromatin folding in Drosophila. We observed that repressed TADs form a succession of discrete nanocompartments, interspersed by less condensed active regions. Single-cell analysis revealed a consistent TAD-based physical compartmentalization of the chromatin fiber, with some degree of heterogeneity in intra-TAD conformations and in cis and trans inter-TAD contact events. These results indicate that TADs are fundamental 3D genome units that engage in dynamic higher-order inter-TAD connections. This domain-based architecture is likely to play a major role in regulatory transactions during DNA-dependent processes. |
format | Online Article Text |
id | pubmed-5829972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58299722018-03-02 TADs are 3D structural units of higher-order chromosome organization in Drosophila Szabo, Quentin Jost, Daniel Chang, Jia-Ming Cattoni, Diego I. Papadopoulos, Giorgio L. Bonev, Boyan Sexton, Tom Gurgo, Julian Jacquier, Caroline Nollmann, Marcelo Bantignies, Frédéric Cavalli, Giacomo Sci Adv Research Articles Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear. Using a combination of Hi-C, three-dimensional (3D) fluorescent in situ hybridization, super-resolution microscopy, and polymer modeling, we provide an integrative view of chromatin folding in Drosophila. We observed that repressed TADs form a succession of discrete nanocompartments, interspersed by less condensed active regions. Single-cell analysis revealed a consistent TAD-based physical compartmentalization of the chromatin fiber, with some degree of heterogeneity in intra-TAD conformations and in cis and trans inter-TAD contact events. These results indicate that TADs are fundamental 3D genome units that engage in dynamic higher-order inter-TAD connections. This domain-based architecture is likely to play a major role in regulatory transactions during DNA-dependent processes. American Association for the Advancement of Science 2018-02-28 /pmc/articles/PMC5829972/ /pubmed/29503869 http://dx.doi.org/10.1126/sciadv.aar8082 Text en Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Szabo, Quentin Jost, Daniel Chang, Jia-Ming Cattoni, Diego I. Papadopoulos, Giorgio L. Bonev, Boyan Sexton, Tom Gurgo, Julian Jacquier, Caroline Nollmann, Marcelo Bantignies, Frédéric Cavalli, Giacomo TADs are 3D structural units of higher-order chromosome organization in Drosophila |
title | TADs are 3D structural units of higher-order chromosome organization in Drosophila |
title_full | TADs are 3D structural units of higher-order chromosome organization in Drosophila |
title_fullStr | TADs are 3D structural units of higher-order chromosome organization in Drosophila |
title_full_unstemmed | TADs are 3D structural units of higher-order chromosome organization in Drosophila |
title_short | TADs are 3D structural units of higher-order chromosome organization in Drosophila |
title_sort | tads are 3d structural units of higher-order chromosome organization in drosophila |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829972/ https://www.ncbi.nlm.nih.gov/pubmed/29503869 http://dx.doi.org/10.1126/sciadv.aar8082 |
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