Inter3D:Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription  

作　　者：Tianyi Ding Shaliu Fu Xiaoyu Zhang Fan Yang Jixing Zhang Haowen Xu Jiaqi Yang Chaoqun Chen Yibing Shi Yiran Bai Wannian Li Xindi Chang Shanjin Wang Chao Zhang Qi Liu He Zhang 

机构地区：[1]State Key Laboratory of Cardiology and Medical Innovation Center,Institute for Regenerative Medicine,Shanghai East Hospital,Frontier Science Research Center for Stem Cells,School of Life Science and Technology,Tongji University,Shanghai 200092,China [2]Jiangxi Province Key Laboratory of Organ Development and Epigenetics,Clinical Medical Research Center,Affiliated Hospital of Jinggangshan University,Medical Department of Jinggangshan University,Ji'an 343009,China [3]School of Life Science,Jinggangshan University,Ji'an 343009,China

出　　处：《Genomics, Proteomics & Bioinformatics》2024年第3期69-84,共16页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.82372705 and 31870748);the Shanghai Oriental Elite Project(Grant No.2000152009);the National Key R&D Program of China(Grant No.2017YFE0196300);the Shanghai Natural Science Foundation(Grant No.22ZR1466100);the Fundamental Research Funds for the Central Universities(Grant No.22120230292);the China Postdoctoral Science Foundation(Grant Nos.2023M742651 and GZC20231946);the Shuguang Project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation(Grant No.17SG19);the Outstanding Yong Medical Scholar of Shanghai Municipal Commission of Health and Family Planning(Grant No.2017YQ067);the Outstanding Yong Scholar Grant of Tongji University(Grant No.PA2019000239);the Startup Funding of Frontier Science Research Center for Stem Cells&Shanghai East Hospital of Tongji University(Grant No.DFRC2019003),China.

摘　　要：Topologically associating domain(TAD)reorganization commonly occurs in the cell nucleus and contributes to gene activation and inhibition through the separation or fusion of adjacent TADs.However,functional genes impacted by TAD alteration and the underlying mechanism of TAD reorganization regulating gene transcription remain to be fully elucidated.Here,we first developed a novel approach termed Inter3D to specifically identify genes regulated by TAD reorganization.Our study revealed that the segregation of TADs led to the disruption of intrachromosomal looping at the myosin light chain 12B(MYL12B)locus,via the meticulous reorganization of TADs mediating epigenomic landscapes within tumor cells,thereby exhibiting a significant correlation with the down-regulation of its transcriptional activity.Conversely,the fusion of TADs facilitated intrachromosomal interactions,suggesting a potential association with the activation of cytochrome P450 family 27 subfamily B member 1(CYP27B1).Our study provides comprehensive insight into the capture of TAD rearrangement-mediated gene loci and moves toward understanding the functional role of TAD reorganization in gene transcription.The Inter3D pipeline developed in this study is freely available at https://github.com/bm2-lab/inter3D and https://ngdc.cncb.ac.cn/biocode/tool/BT7399.

关 键 词：Topologically associating domain Inter3D Chromosomal loop Gene transcription Cancer 

分 类 号：Q811.4[生物学—生物工程]