Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons  

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 

机构地区：[1]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 [2]Shenzhen Key Laboratory of Drug Addiction,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China [3]Department of Psychiatry,West China Hospital of Sichuan University,Chengdu 610041,China [4]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 [5]State Key Laboratory of Agricultural Microbiology,Hubei Hongshan Laboratory,Huazhong Agricultural University,Wuhan 430070,China

出　　处：《Genomics, Proteomics & Bioinformatics》2023年第3期551-572,共22页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Grant Nos.82071494,81871043,32000719,and 81272459);the 1.3.5 Project for Disciplines of Excellence of West China Hospital of Sichuan University(Grant No.ZYGD23011);the China Postdoctoral Science Foundation(Grant No.2021M702362);the PostDoctor Research Project,West China Hospital,Sichuan University(Grant No.2020HXBH010);the Sichuan Science and Technology Program(Grant No.23NSFSC2884);the Science,Technology and Innovation Commission of Shenzhen Municipality(Grant No.ZDSYS20190902093601675),China.

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 conformation 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.

关 键 词：MORPHINE Rhesus monkey Chromatin spatial architecture Topologically associated domain Loop 

分 类 号：Q753[生物学—分子生物学]