50 / 2024-10-12 13:38:31

The three-dimensional genome mediated mechanism underlying tumorigenesis

Topologically associating domain,DNA-RNA triplex,Transcriptional factor,Long-noncoding RNA,Tumorigenesis,Chromosomal loop

The three-dimensional genome mediated mechanism underlying tumorigenesis

Tianyi Ding, Xiaoyu Zhang, He Zhang<sup>1, *

1</sup> School of Life Sciences and Technology, Tongji University

^* zhanghe@tongji.edu.cn



Complicated higher-order chromatin architecture creates a dynamic spatial epigenomic landscape that regulates gene transcription through both DNA-DNA interactions and DNA-RNA hybridization. However, the identification of functional genes impacted by these intricate mechanisms in tumorigenesis remains incompletely elucidated. Here, we first developed a novel approach termed Inter3D, which specifically captures functional genes or lncRNAs regulated by TAD and chromosomal looping. Our findings highlight the role of chromatin accessibility in facilitating PHB2 to orchestrate the transcription of an oncogenic CANT2 lncRNA and the coding tumor-suppressor gene CCBE1. Moreover, PPIA serves as an anchor to recruit GAU1 lncRNA, promoting the formation of the SENP5/GAU1 DNA-lncRNA triplex, which drives tumorigenesis in vitro and in vivo. Our study provides comprehensive insights into the capture of 3D genome rearrangement-mediated gene loci and moves toward understanding the functional role of chromatin structure in tumorigenesis.



Keywords: Topologically associating domain, Chromosomal loop, DNA-RNA triplex, Transcriptional factor, Long-noncoding RNA, Tumorigenesis