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TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations

BACKGROUND: Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tr...

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Autores principales: Cheng, Yubao, Liu, Miao, Hu, Mengwei, Wang, Siyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574027/
https://www.ncbi.nlm.nih.gov/pubmed/34749781
http://dx.doi.org/10.1186/s13059-021-02523-8
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author Cheng, Yubao
Liu, Miao
Hu, Mengwei
Wang, Siyuan
author_facet Cheng, Yubao
Liu, Miao
Hu, Mengwei
Wang, Siyuan
author_sort Cheng, Yubao
collection PubMed
description BACKGROUND: Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tracing lead to the discovery of cohesin-independent TAD-like structures, also known as single-cell domains, which are highly variant self-interacting chromatin domains with boundaries that occasionally overlap with TAD boundaries but tend to differ among single cells and among single chromosome copies. Recent computational modeling studies suggest that epigenetic interactions may underlie the formation of the single-cell domains. RESULTS: Here we use chromatin tracing to visualize in female human cells the fine-scale chromatin folding of inactive and active X chromosomes, which are known to have distinct global epigenetic landscapes and distinct population-averaged TAD profiles, with inactive X chromosomes largely devoid of TADs and cohesin. We show that both inactive and active X chromosomes possess highly variant single-cell domains across the same genomic region despite the fact that only active X chromosomes show clear TAD structures at the population level. These X chromosome single-cell domains exist in distinct cell lines. Perturbations of major epigenetic components and transcription mostly do not affect the frequency or strength of the single-cell domains. Increased chromatin compaction of inactive X chromosomes occurs at a length scale above that of the single-cell domains. CONCLUSIONS: In sum, this study suggests that single-cell domains are genome architecture building blocks independent of the tested major epigenetic components. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02523-8.
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spelling pubmed-85740272021-11-08 TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations Cheng, Yubao Liu, Miao Hu, Mengwei Wang, Siyuan Genome Biol Research BACKGROUND: Topologically associating domains (TADs) are important building blocks of three-dimensional genome architectures. The formation of TADs has been shown to depend on cohesin in a loop-extrusion mechanism. Recently, advances in an image-based spatial genomics technique known as chromatin tracing lead to the discovery of cohesin-independent TAD-like structures, also known as single-cell domains, which are highly variant self-interacting chromatin domains with boundaries that occasionally overlap with TAD boundaries but tend to differ among single cells and among single chromosome copies. Recent computational modeling studies suggest that epigenetic interactions may underlie the formation of the single-cell domains. RESULTS: Here we use chromatin tracing to visualize in female human cells the fine-scale chromatin folding of inactive and active X chromosomes, which are known to have distinct global epigenetic landscapes and distinct population-averaged TAD profiles, with inactive X chromosomes largely devoid of TADs and cohesin. We show that both inactive and active X chromosomes possess highly variant single-cell domains across the same genomic region despite the fact that only active X chromosomes show clear TAD structures at the population level. These X chromosome single-cell domains exist in distinct cell lines. Perturbations of major epigenetic components and transcription mostly do not affect the frequency or strength of the single-cell domains. Increased chromatin compaction of inactive X chromosomes occurs at a length scale above that of the single-cell domains. CONCLUSIONS: In sum, this study suggests that single-cell domains are genome architecture building blocks independent of the tested major epigenetic components. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-021-02523-8. BioMed Central 2021-11-08 /pmc/articles/PMC8574027/ /pubmed/34749781 http://dx.doi.org/10.1186/s13059-021-02523-8 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
Cheng, Yubao
Liu, Miao
Hu, Mengwei
Wang, Siyuan
TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
title TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
title_full TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
title_fullStr TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
title_full_unstemmed TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
title_short TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
title_sort tad-like single-cell domain structures exist on both active and inactive x chromosomes and persist under epigenetic perturbations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8574027/
https://www.ncbi.nlm.nih.gov/pubmed/34749781
http://dx.doi.org/10.1186/s13059-021-02523-8
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