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<p>Alterations in 3D chromatin conformation may disrupt the interplay between promoters and distal enhancers. How gene regulatory circuits are reshaped during ionizing radiation-induced tumorigenesis remains unclear, and little is known about the mediators that drive these processes. To decipher the chromatin alterations in radiation-induced lung cancer, we performed ATAC-seq, RNA-seq and Hi-C analyses of human bronchial epithelial cells and corresponding radiation-induced malignantly transformed cell lines. We found that this malignant transformation is accompanied by chromatin switching from the inactive B compartment to the active A compartment, an increased number of TADs and gained ATAC-seq peaks that mediate new distal chromatin contacts. We identified tumour protein 63 (TP63) as a mediator of new chromatin-accessible sites that anchor tumour-specific chromatin contacts in radiation-induced tumour cells. A TP63-mediated accessible chromatin site anchors a tumour-specific TAD boundary and multiple tumour-specific chromatin loops, which might underlie <i>MYC</i> oncogene activation during malignant transformation.</p>

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TP63 mediates the generation of tumour-specific chromatin loops that underlie MYC activation in radiation-induced tumorigenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Qiaowei Liu,
  • Shuai Jiang,
  • Xiang Xu,
  • Kang Xu,
  • Yawen Luo,
  • Zongyuan Yu,
  • Meida Xiang,
  • Zhouyang Xu,
  • Lijie Wang,
  • Sujie Zhang,
  • Haitao Tao,
  • Xuhui Yang,
  • Chongbo Jiang,
  • Xiaoguang Qi,
  • Hao Li,
  • Yiming Gao,
  • Yao Li,
  • Shihui Fu,
  • Pingkun Zhou,
  • Xiaochen Bo,
  • Hebing Chen,
  • Xiaohua Chen,
  • Yi Hu

摘要

Alterations in 3D chromatin conformation may disrupt the interplay between promoters and distal enhancers. How gene regulatory circuits are reshaped during ionizing radiation-induced tumorigenesis remains unclear, and little is known about the mediators that drive these processes. To decipher the chromatin alterations in radiation-induced lung cancer, we performed ATAC-seq, RNA-seq and Hi-C analyses of human bronchial epithelial cells and corresponding radiation-induced malignantly transformed cell lines. We found that this malignant transformation is accompanied by chromatin switching from the inactive B compartment to the active A compartment, an increased number of TADs and gained ATAC-seq peaks that mediate new distal chromatin contacts. We identified tumour protein 63 (TP63) as a mediator of new chromatin-accessible sites that anchor tumour-specific chromatin contacts in radiation-induced tumour cells. A TP63-mediated accessible chromatin site anchors a tumour-specific TAD boundary and multiple tumour-specific chromatin loops, which might underlie MYC oncogene activation during malignant transformation.