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The hierarchical folding dynamics of topologically associating domains are closely related to transcriptional abnormalities in cancers

Authors :
Hao Hong
Yang Ding
Yuanping Yang
Yu Sun
Yang Zheng
Qi Jiang
Xiang Xu
Kang Xu
Hao Li
Huan Tao
Yaru Li
Guifang Du
Xin Huang
Xuemei Bai
Hebing Chen
Yinyin Li
Shuai Jiang
Yaoshen Li
Jingbo Gan
Junting Wang
Cheng Li
Xiaochen Bo
Longteng Wang
Source :
Computational and Structural Biotechnology Journal, Vol 19, Iss, Pp 1684-1693 (2021), Computational and Structural Biotechnology Journal
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

Graphical abstract<br />Highlights • The hierarchical levels of TAD boundaries were tissue- and cell type-specific. • The TAD nesting level of genes in tumors is different from that in normal tissue. • Hierarchical TAD level of genes is related to abnormal transcription and prognosis in cancers.<br />Recent studies have shown that the three-dimensional (3D) structure of chromatin is associated with cancer progression. However, the roles of the 3D genome structure and its dynamics in cancer remains largely unknown. In this study, we investigated hierarchical topologically associating domain (TAD) structures in cancers and defined a “TAD hierarchical score (TH score)” for genes, which allowed us to assess the TAD nesting level of all genes in a simplified way. We demonstrated that the TAD nesting levels of genes in a tumor differ from those in normal tissue. Furthermore, the hierarchical TAD level dynamics were related to transcriptional changes in cancer, and some of the genes in which the hierarchical level was altered were significantly related to the prognosis of cancer patients. Overall, the results of this study suggest that the folding dynamics of TADs are closely related to transcriptional abnormalities in cancers, emphasizing that the function of hierarchical chromatin organization goes beyond simple chromatin packaging efficiency.

Details

ISSN :
20010370
Volume :
19
Database :
OpenAIRE
Journal :
Computational and Structural Biotechnology Journal
Accession number :
edsair.doi.dedup.....ba7d382c8aee5d0ae8db3c40f6a68628