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

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.

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Journal
Nature Communications
Published
2025-09-30
DOI
https://doi.org/10.1038/s41467-025-63754-y
Primary Topic
Genomics and Chromatin Dynamics
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Qiaowei Liu, Xiaoguang Qi, Yawen Luo, Shuai Jiang et al.
Nature Communications
Genomics and Chromatin Dynamics
article

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

Qiaowei Liu, Xiaoguang Qi, Yawen Luo, Shuai Jiang, Yi Hu, Shihui Fu, Yu Zhou, Xiaochen Bo, Yiming Gao, Ping‐Kun Zhou, Meida Xiang, Hebing Chen, Haitao Tao, Chunmiao Jiang, Xuhui Yang, Xiaohua Chen, Yao Li, Hao Li, Lijie Wang, Xiang Xu, Zhihua Xu, Sujie Zhang, Kang Xu
article en

Abstract

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.

Nature CommunicationsVol. 16(1)
Academy of Military Medical Sciences (CN), Chinese PLA General Hospital (CN), National Center of Biomedical Analysis (CN), Beijing Radiation Center (CN), Hainan 301 Hospital (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, National Key Research and Development Program of China
Openalex Percentile: Top 76%
Genomics and Chromatin Dynamics
DOIOpen Access PDFOpenAlex
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