Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

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外文摘要：The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of chromatin.Morphine-induced aberrant gene networks of neurons have been extensively investigated;however,how morphine impacts the 3D genomic architecture of neurons is still unknown.Here,we applied digestion-ligation-only high-throughput chromosome conforma-tion capture(DLO Hi-C)technology to investigate the effects of morphine on the 3D chromatin architecture of primate cortical neurons.After receiving continuous morphine administration for 90 days on rhesus monkeys,we discovered that morphine re-arranged chromosome territories,with a total of 391 segmented compartments being switched.Morphine altered over half of the detected topologically associated domains(TADs),most of which exhibited a variety of shifts,followed by separating and fusing types.Analysis of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential loops.Moreover,all identified differentially expressed genes from the RNA sequencing data were mapped to the specific TAD boundaries or differential loops,and were further validated for changed expression.Collectively,an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine effects.Our finding provides critical hubs connecting chromosome spatial organization and gene networks associated with the morphine effects in humans.

外文关键词：

MorphineRhesus monkeyChromatin spatial architectureTopologically associated domainLoop

作者：

Liang Wang、Xiaojie Wang、Chunqi Liu、Wei Xu、Weihong Kuang、Qian Bu、Hongchun Li、Ying Zhao、Linhong Jiang、Yaxing Chen、Feng Qin、Shu Li、Qinfan Wei、Xiaocong Liu、Bin Liu、Yuanyuan Chen、Yanping Dai、Hongbo Wang、Jingwei Tian、Gang Cao、Yinglan Zhao、Xiaobo Cen

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作者单位：

National Chengdu Center for Safety Evaluation of Drugs,State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy,West China Hospital of Sichuan University,Chengdu 610041,China

Shenzhen Key Laboratory of Drug Addiction,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China

Department of Psychiatry,West China Hospital of Sichuan University,Chengdu 610041,China

School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China

State Key Laboratory of Agricultural Microbiology,Hubei Hongshan Laboratory,Huazhong Agricultural University,Wuhan 430070,China

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基金：

grants from the National Natural Science Foundation of Chinagrants from the National Natural Science Foundation of Chinagrants from the National Natural Science Foundation of Chinagrants from the National Natural Science Foundation of China1.3.5 Project for Disciplines of Excellence of West China Hospital of Sichuan UniversityChina Postdoctoral Science FoundationPost-Doctor Research Project,West China Hospital,Sichuan UniversitySichuan Science and Technology ProgramScience,Technology and Innovation Commission of Shenzhen Municipality,China

项目编号：

82071494818710433200071981272459ZYGD230112021M7023622020HXBH01023NSFSC2884ZDSYS20190902093601675

出版年：

2023

DOI：

10.1016/j.gpb.2023.03.003

基因组蛋白质组与生物信息学报(英文版)

中国科学院北京基因组研究所

基因组蛋白质组与生物信息学报(英文版)

CSTPCDCSCD

影响因子：0.495

ISSN：1672-0229

年,卷(期)：2023.21(3)

参考文献量87