Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion

Three-dimensional genome organization has been increasingly recognized as an important determinant of the precise regulation of gene expression in mammalian cells, yet the relationship between gene transcriptional activity and spatial subcompartment positioning is still not fully comprehended. Here,...

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Main Authors: Zihang Yin, Shuang Cui, Song Xue, Yufan Xie, Yefan Wang, Chengling Zhao, Zhiyu Zhang, Tao Wu, Guojun Hou, Wuming Wang, Sheila Q. Xie, Yue Wu, Ya Guo
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/12/8/1058
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author Zihang Yin
Shuang Cui
Song Xue
Yufan Xie
Yefan Wang
Chengling Zhao
Zhiyu Zhang
Tao Wu
Guojun Hou
Wuming Wang
Sheila Q. Xie
Yue Wu
Ya Guo
author_facet Zihang Yin
Shuang Cui
Song Xue
Yufan Xie
Yefan Wang
Chengling Zhao
Zhiyu Zhang
Tao Wu
Guojun Hou
Wuming Wang
Sheila Q. Xie
Yue Wu
Ya Guo
author_sort Zihang Yin
collection DOAJ
description Three-dimensional genome organization has been increasingly recognized as an important determinant of the precise regulation of gene expression in mammalian cells, yet the relationship between gene transcriptional activity and spatial subcompartment positioning is still not fully comprehended. Here, we first utilized genome-wide Hi-C data to infer eight types of subcompartment (labeled A1, A2, A3, A4, B1, B2, B3, and B4) in mouse embryonic stem cells and four primary differentiated cell types, including thymocytes, macrophages, neural progenitor cells, and cortical neurons. Transitions of subcompartments may confer gene expression changes in different cell types. Intriguingly, we identified two subsets of subcompartments defined by higher gene density and characterized by strongly looped contact domains, named common A1 and variable A1, respectively. We revealed that common A1, which includes highly expressed genes and abundant housekeeping genes, shows a ~2-fold higher gene density than the variable A1, where cell type-specific genes are significantly enriched. Thus, our study supports a model in which both types of genomic loci with constitutive and regulatory high transcriptional activity can drive the subcompartment A1 formation. Special chromatin subcompartment arrangement and intradomain interactions may, in turn, contribute to maintaining proper levels of gene expression, especially for regulatory non-housekeeping genes.
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spelling doaj.art-6d1279a105d742fd97d9b639488de7fa2023-12-01T01:37:56ZengMDPI AGBiology2079-77372023-07-01128105810.3390/biology12081058Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop ExtrusionZihang Yin0Shuang Cui1Song Xue2Yufan Xie3Yefan Wang4Chengling Zhao5Zhiyu Zhang6Tao Wu7Guojun Hou8Wuming Wang9Sheila Q. Xie10Yue Wu11Ya Guo12Sheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaDepartment of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaShanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai 200001, ChinaCUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaMRC London Institute of Medical Sciences, London W12 0NN, UKDepartment of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaSheng Yushou Center of Cell Biology and Immunology, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaThree-dimensional genome organization has been increasingly recognized as an important determinant of the precise regulation of gene expression in mammalian cells, yet the relationship between gene transcriptional activity and spatial subcompartment positioning is still not fully comprehended. Here, we first utilized genome-wide Hi-C data to infer eight types of subcompartment (labeled A1, A2, A3, A4, B1, B2, B3, and B4) in mouse embryonic stem cells and four primary differentiated cell types, including thymocytes, macrophages, neural progenitor cells, and cortical neurons. Transitions of subcompartments may confer gene expression changes in different cell types. Intriguingly, we identified two subsets of subcompartments defined by higher gene density and characterized by strongly looped contact domains, named common A1 and variable A1, respectively. We revealed that common A1, which includes highly expressed genes and abundant housekeeping genes, shows a ~2-fold higher gene density than the variable A1, where cell type-specific genes are significantly enriched. Thus, our study supports a model in which both types of genomic loci with constitutive and regulatory high transcriptional activity can drive the subcompartment A1 formation. Special chromatin subcompartment arrangement and intradomain interactions may, in turn, contribute to maintaining proper levels of gene expression, especially for regulatory non-housekeeping genes.https://www.mdpi.com/2079-7737/12/8/1058genome foldingA/B compartmentsTADscontact domainschromatin loopingtissue-specific gene
spellingShingle Zihang Yin
Shuang Cui
Song Xue
Yufan Xie
Yefan Wang
Chengling Zhao
Zhiyu Zhang
Tao Wu
Guojun Hou
Wuming Wang
Sheila Q. Xie
Yue Wu
Ya Guo
Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion
Biology
genome folding
A/B compartments
TADs
contact domains
chromatin looping
tissue-specific gene
title Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion
title_full Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion
title_fullStr Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion
title_full_unstemmed Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion
title_short Identification of Two Subsets of Subcompartment A1 Associated with High Transcriptional Activity and Frequent Loop Extrusion
title_sort identification of two subsets of subcompartment a1 associated with high transcriptional activity and frequent loop extrusion
topic genome folding
A/B compartments
TADs
contact domains
chromatin looping
tissue-specific gene
url https://www.mdpi.com/2079-7737/12/8/1058
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