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

Abstract 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 chro...

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Autores principales:	Yubao Cheng, Miao Liu, Mengwei Hu, Siyuan Wang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Topologically associating domain (TAD) TAD-like structure Single-cell domain X chromosome X inactivation Chromatin folding Biology (General) QH301-705.5 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/80d1bcada4eb43aa81375ace6e1ae83c
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spelling	oai:doaj.org-article:80d1bcada4eb43aa81375ace6e1ae83c2021-11-14T12:42:56ZTAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations10.1186/s13059-021-02523-81474-760Xhttps://doaj.org/article/80d1bcada4eb43aa81375ace6e1ae83c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13059-021-02523-8https://doaj.org/toc/1474-760XAbstract 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.Yubao ChengMiao LiuMengwei HuSiyuan WangBMCarticleTopologically associating domain (TAD)TAD-like structureSingle-cell domainX chromosomeX inactivationChromatin foldingBiology (General)QH301-705.5GeneticsQH426-470ENGenome Biology, Vol 22, Iss 1, Pp 1-26 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Topologically associating domain (TAD) TAD-like structure Single-cell domain X chromosome X inactivation Chromatin folding Biology (General) QH301-705.5 Genetics QH426-470
spellingShingle	Topologically associating domain (TAD) TAD-like structure Single-cell domain X chromosome X inactivation Chromatin folding Biology (General) QH301-705.5 Genetics QH426-470 Yubao Cheng Miao Liu Mengwei Hu Siyuan Wang TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations
description	Abstract 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.
format	article
author	Yubao Cheng Miao Liu Mengwei Hu Siyuan Wang
author_facet	Yubao Cheng Miao Liu Mengwei Hu Siyuan Wang
author_sort	Yubao Cheng
title	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_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_sort	tad-like single-cell domain structures exist on both active and inactive x chromosomes and persist under epigenetic perturbations
publisher	BMC
publishDate	2021
url	https://doaj.org/article/80d1bcada4eb43aa81375ace6e1ae83c
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TAD-like single-cell domain structures exist on both active and inactive X chromosomes and persist under epigenetic perturbations

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