Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation
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Published:2022-10-04
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Lin DaORCID, Xu Weize, Hong Ping, Wu ChengchaoORCID, Zhang Zhihui, Zhang Siheng, Xing Lingyu, Yang Bing, Zhou Wei, Xiao Qin, Wang Jinyue, Wang Cong, He Yu, Chen Xi, Cao Xiaojian, Man Jiangwei, Reheman Aikebaier, Wu Xiaofeng, Hao Xingjie, Hu Zhe, Chen ChunliORCID, Cao Zimeng, Yin Rong, Fu Zhen F.ORCID, Zhou Rong, Teng ZhaoweiORCID, Li GuoliangORCID, Cao GangORCID
Abstract
AbstractImmunocytes dynamically reprogram their gene expression profiles during differentiation and immunoresponse. However, the underlying mechanism remains elusive. Here, we develop a single-cell Hi-C method and systematically delineate the 3D genome and dynamic epigenetic atlas of macrophages during these processes. We propose “degree of disorder” to measure genome organizational patterns inside topologically-associated domains, which is correlated with the chromatin epigenetic states, gene expression, and chromatin structure variability in individual cells. Furthermore, we identify that NF-κB initiates systematic chromatin conformation reorganization upon Mycobacterium tuberculosis infection. The integrated Hi-C, eQTL, and GWAS analysis depicts the atlas of the long-range target genes of mycobacterial disease susceptible loci. Among these, the SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 3D genome structure of immunocytes and sheds insights into the order of genome organization and the coordinated gene transcription during immunoresponse.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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