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Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons

Genomics, Proteomics & Bioinformatics 2023年第3期21卷 551-572页

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 National Chengdu Center for Safety Evaluation of Drugs State Key Laboratory of Biotherapy/Collaborative Innovation Center for BiotherapyWest China Hospital of Sichuan UniversityChengdu 610041China Shenzhen Key Laboratory of Drug Addiction Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Psychiatry West China Hospital of Sichuan UniversityChengdu 610041China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China

The expression of linear DNA sequence is precisely regulated by the three-dimensional(3D)architecture of ***-induced aberrant gene networks of neurons have been extensively investigated;however,how morphine impacts the 3D genomic architecture of neurons is still ***,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 *** 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 *** altered over half of the detected topologically associated domains(TADs),most of which exhibited a variety of shifts,followed by separating and fusing *** of the looping events at kilobase-scale resolution revealed that morphine increased not only the number but also the length of differential ***,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 ***,an altered 3D genomic architecture of cortical neurons may regulate the gene networks associated with morphine *** 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

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3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3150-3164页

作者： Lina Xu Lianhong Yin Yan Qi Xuemei Tan Meng Gao Jinyong Peng College of Pharmacy Dalian Medical UniversityDalian 116044China Key Laboratory for Basic and Applied Research on Pharmacodynamics Substances of Traditional Chinese Medicine of Liaoning Province Dalian Medical UniversityDalian 116044China National-Local Joint Engineering Research Center for Drug Development(R&D)of Neurodegenerative Diseases Dalian Medical UniversityDalian 116044China

The three-dimensional(3D)conformation of chromatin is integral to the precise regulation of gene *** 3D genome and genomic variations in non-alcoholic fatty liver disease(NAFLD)are largely unknown,despite their key roles in cellular function and physiological *** chromosome conformation capture(Hi-C),Nanopore sequencing,and RNA-sequencing(RNA-seq)assays were performed on the liver of normal and NAFLD mice.A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments,topologically associated domains(TADs),and chromatin loops by Hi-C,and whole genome sequencing identifying structural variations(SVs)and copy number variations(CNVs)by Nanopore *** identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements,between normal and NAFLD mice,and revealed gene dysregulation frequently accompanied by these *** target genes were identified in NAFLD,impacted by genetic rearrangements and spatial organization *** data provide a high-resolution 3D genome interaction resource for NAFLD investigations,revealed the relationship among genetic rearrangements,spatial organization disruption,and gene regulation,and identified candidate genes associated with these variations implicated in the pathogenesis of *** newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

关键词： 3D genome Chromatin looping topologically associated domain Transcriptome Whole-genome sequencing

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