Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis
The high‐order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi‐omics data on the large variety of...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-02-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13127 |
| _version_ | 1798018869963522048 |
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| author | Yue Xue Ying Yang Hao Tian Hui Quan Sirui Liu Ling Zhang Lu Yang Haichuan Zhu Hong Wu Yi Qin Gao |
| author_facet | Yue Xue Ying Yang Hao Tian Hui Quan Sirui Liu Ling Zhang Lu Yang Haichuan Zhu Hong Wu Yi Qin Gao |
| author_sort | Yue Xue |
| collection | DOAJ |
| description | The high‐order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi‐omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase‐sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic, and transcriptional properties: CGI‐rich and CGI‐poor domains. Through an integrated analysis of chromatin structure, DNA methylation, and RNA sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes and have an increased number of DNA methylation differences and transcriptional‐level differences, compared with in noncancer cells. We also compared the structural features among carcinogenesis, senescence, and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer‐related properties. In summary, chromatin structure, DNA methylation, and gene expression, as well as their changes observed in several types of cancers, show a dependence on multiscale DNA sequence heterogeneity. |
| first_indexed | 2024-04-11T16:31:18Z |
| format | Article |
| id | doaj.art-556d702c930a4a1599ff8297f904b2f7 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-04-11T16:31:18Z |
| publishDate | 2022-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-556d702c930a4a1599ff8297f904b2f72022-12-22T04:14:01ZengWileyMolecular Oncology1574-78911878-02612022-02-0116369971610.1002/1878-0261.13127Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesisYue Xue0Ying Yang1Hao Tian2Hui Quan3Sirui Liu4Ling Zhang5Lu Yang6Haichuan Zhu7Hong Wu8Yi Qin Gao9Beijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaBeijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaBeijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaBeijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaBeijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaBeijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaThe MOE Key Laboratory of Cell Proliferation and Differentiation School of Life Sciences Peking University Beijing ChinaThe MOE Key Laboratory of Cell Proliferation and Differentiation School of Life Sciences Peking University Beijing ChinaThe MOE Key Laboratory of Cell Proliferation and Differentiation School of Life Sciences Peking University Beijing ChinaBeijing National Laboratory for Molecular Sciences College of Chemistry and Molecular Engineering Peking University Beijing ChinaThe high‐order chromatin structure, together with DNA methylation and other epigenetic marks, plays a vital role in gene regulation and displays abnormal status in cancer cells. Theoretical analyses are expected to provide a more unified understanding of the multi‐omics data on the large variety of samples, and hopefully a common picture of carcinogenesis. In particular, we are interested in the question of whether an underlying origin DNA sequence exists for these epigenetic alterations. The human genome consists of two types of megabase‐sized domain based on the distribution of CpG islands (CGIs) that show distinct structural, epigenetic, and transcriptional properties: CGI‐rich and CGI‐poor domains. Through an integrated analysis of chromatin structure, DNA methylation, and RNA sequencing data, we found that, in carcinogenesis, the two different types of domain display different structural changes and have an increased number of DNA methylation differences and transcriptional‐level differences, compared with in noncancer cells. We also compared the structural features among carcinogenesis, senescence, and mitosis, showing the possible connection between chromatin structure and cell state, which could affect vital cancer‐related properties. In summary, chromatin structure, DNA methylation, and gene expression, as well as their changes observed in several types of cancers, show a dependence on multiscale DNA sequence heterogeneity.https://doi.org/10.1002/1878-0261.13127carcinogenesischromatin structureDNA methylationgene expression dysregulation |
| spellingShingle | Yue Xue Ying Yang Hao Tian Hui Quan Sirui Liu Ling Zhang Lu Yang Haichuan Zhu Hong Wu Yi Qin Gao Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis Molecular Oncology carcinogenesis chromatin structure DNA methylation gene expression dysregulation |
| title | Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis |
| title_full | Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis |
| title_fullStr | Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis |
| title_full_unstemmed | Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis |
| title_short | Computational characterization of domain‐segregated 3D chromatin structure and segmented DNA methylation status in carcinogenesis |
| title_sort | computational characterization of domain segregated 3d chromatin structure and segmented dna methylation status in carcinogenesis |
| topic | carcinogenesis chromatin structure DNA methylation gene expression dysregulation |
| url | https://doi.org/10.1002/1878-0261.13127 |
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