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  • 标题:The hierarchical folding dynamics of topologically associating domains are closely related to transcriptional abnormalities in cancers
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  • 作者:Guifang Du ; Hao Li ; Yang Ding
  • 期刊名称:Computational and Structural Biotechnology Journal
  • 印刷版ISSN:2001-0370
  • 出版年度:2021
  • 卷号:19
  • 页码:1684-1693
  • DOI:10.1016/j.csbj.2021.03.018
  • 出版社:Computational and Structural Biotechnology Journal
  • 摘要: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.
  • 关键词:Hierarchical TAD ; Cancers ; Transcriptional regulation ; TH score ; Hi-C ; Colorectal cancer
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