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 morp...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.展开更多
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)+3 种基金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.
文摘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.
