Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes
Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interaction...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Genomics, Proteomics & Bioinformatics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1672022923000049 |
| _version_ | 1797372025420906496 |
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| author | Yan Zhang Jingwen Zhang Wei Zhang Mohan Wang Shuangqi Wang Yao Xu Lun Zhao Xingwang Li Guoliang Li |
| author_facet | Yan Zhang Jingwen Zhang Wei Zhang Mohan Wang Shuangqi Wang Yao Xu Lun Zhao Xingwang Li Guoliang Li |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system and generated high-resolution chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste homolog 2 (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET). Analysis showed that EZH2/H3K27me3-mediated interactions further repressed target genes, either through loops or domains, and their distributions along the genome were distinct from and complementary to those associated with RNAPII. Cancer-related genes were highly enriched with chromatin interactions, and chromatin interactions specific to the A549 cell line were associated with oncogenes and tumor suppressor genes, such as additional repressive interactions on FOXO4 and promoter–promoter interactions between NF1 and RNF135. Knockout of an anchor associated with chromatin interactions reversed the dysregulation of cancer-related genes, suggesting that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings demonstrate the 3D landscape and gene regulatory relationships of the lung cancer genome. |
| first_indexed | 2024-03-08T18:29:29Z |
| format | Article |
| id | doaj.art-1e3fe36efa1a4042a00471f3705b5ee3 |
| institution | Directory Open Access Journal |
| issn | 1672-0229 |
| language | English |
| last_indexed | 2024-03-08T18:29:29Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Genomics, Proteomics & Bioinformatics |
| spelling | doaj.art-1e3fe36efa1a4042a00471f3705b5ee32023-12-30T04:42:56ZengElsevierGenomics, Proteomics & Bioinformatics1672-02292023-06-01213573588Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related GenesYan Zhang0Jingwen Zhang1Wei Zhang2Mohan Wang3Shuangqi Wang4Yao Xu5Lun Zhao6Xingwang Li7Guoliang Li8National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China; Hubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China; Hubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China; Hubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China; Hubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, Huazhong Agricultural University, Wuhan 430070, ChinaHubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, ChinaNational Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China; Hubei Key Laboratory of Agricultural Bioinformatics and Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, Huazhong Agricultural University, Wuhan 430070, China; Corresponding author.Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system and generated high-resolution chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste homolog 2 (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET). Analysis showed that EZH2/H3K27me3-mediated interactions further repressed target genes, either through loops or domains, and their distributions along the genome were distinct from and complementary to those associated with RNAPII. Cancer-related genes were highly enriched with chromatin interactions, and chromatin interactions specific to the A549 cell line were associated with oncogenes and tumor suppressor genes, such as additional repressive interactions on FOXO4 and promoter–promoter interactions between NF1 and RNF135. Knockout of an anchor associated with chromatin interactions reversed the dysregulation of cancer-related genes, suggesting that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings demonstrate the 3D landscape and gene regulatory relationships of the lung cancer genome.http://www.sciencedirect.com/science/article/pii/S1672022923000049Lung cancer3D genomeChIA-PETChromatin interactionDysregulation |
| spellingShingle | Yan Zhang Jingwen Zhang Wei Zhang Mohan Wang Shuangqi Wang Yao Xu Lun Zhao Xingwang Li Guoliang Li Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes Genomics, Proteomics & Bioinformatics Lung cancer 3D genome ChIA-PET Chromatin interaction Dysregulation |
| title | Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes |
| title_full | Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes |
| title_fullStr | Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes |
| title_full_unstemmed | Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes |
| title_short | Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes |
| title_sort | mapping multi factor mediated chromatin interactions to assess dysregulation of lung cancer related genes |
| topic | Lung cancer 3D genome ChIA-PET Chromatin interaction Dysregulation |
| url | http://www.sciencedirect.com/science/article/pii/S1672022923000049 |
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