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 impa...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.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82372705 and 31870748)the Shanghai Oriental Elite Project(Grant No.2000152009)+7 种基金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.
文摘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.
