吗啡重新排列灵长类皮质神经元的染色质空间结构。

IF 11.5 2区 生物学 Q1 GENETICS & HEREDITY Genomics, Proteomics & Bioinformatics Pub Date : 2023-06-01 Epub Date: 2023-05-19 DOI:10.1016/j.gpb.2023.03.003
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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引用次数: 0

摘要

线性DNA序列的表达受到染色质三维结构的精确调控。吗啡诱导的神经元异常基因网络已被广泛研究;然而,吗啡如何影响神经元的3D基因组结构仍然是未知的。在这里,我们应用仅消化连接高通量染色体构象捕获(DLO-Hi-C)技术来研究吗啡对灵长类皮层神经元3D染色质结构的影响。在恒河猴身上连续服用吗啡90天后,我们发现吗啡重新排列了染色体区域,共有391个分段区室被切换。吗啡改变了超过一半的检测到的拓扑相关结构域(TAD),其中大多数表现出各种变化,随后是分离和融合类型。在千碱基尺度分辨率下对回路事件的分析表明,吗啡不仅增加了微分回路的数量,而且增加了微分环路的长度。此外,从RNA测序数据中鉴定的所有差异表达基因都被映射到特定的TAD边界或差异环,并被进一步验证为发生了变化。总的来说,皮层神经元的3D基因组结构的改变可能调节与吗啡效应相关的基因网络。我们的发现提供了连接染色体空间组织和与人类吗啡效应相关的基因网络的关键枢纽。
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Morphine Re-arranges Chromatin Spatial Architecture of Primate Cortical Neurons.

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.

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来源期刊
Genomics, Proteomics & Bioinformatics
Genomics, Proteomics & Bioinformatics Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
14.30
自引率
4.20%
发文量
844
审稿时长
61 days
期刊介绍: Genomics, Proteomics and Bioinformatics (GPB) is the official journal of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China. It aims to disseminate new developments in the field of omics and bioinformatics, publish high-quality discoveries quickly, and promote open access and online publication. GPB welcomes submissions in all areas of life science, biology, and biomedicine, with a focus on large data acquisition, analysis, and curation. Manuscripts covering omics and related bioinformatics topics are particularly encouraged. GPB is indexed/abstracted by PubMed/MEDLINE, PubMed Central, Scopus, BIOSIS Previews, Chemical Abstracts, CSCD, among others.
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