HPV-CCDC106 integration alters local chromosome architecture and hijacks an enhancer by three-dimensional genome structure remodeling in cervical cancer
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved..
Integration of human papillomavirus (HPV) DNA into the human genome is a reputed key driver of cervical cancer. However, the effects of HPV integration on chromatin structural organization and gene expression are largely unknown. We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19. We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome, RNA, chromatin immunoprecipitation and high-throughput chromosome conformation capture (Hi-C) sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis. Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities, with correlation found between three-dimensional (3D) structural change and gene expression. Importantly, HPV integration divided one topologically associated domain (TAD) into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106, with a decrease in PEG3 expression and an increase in CCDC106 expression. This expression dysregulation was further confirmed using 10 samples from our cohort, which exhibited the same HPV-CCDC106 integration. In summary, we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling. Thus, this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Journal of genetics and genomics = Yi chuan xue bao - 47(2020), 8 vom: 01. Aug., Seite 437-450 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cao, Canhui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.07.2021 Date Revised 05.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jgg.2020.05.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315940174 |
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| 100 | 1 | |a Cao, Canhui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HPV-CCDC106 integration alters local chromosome architecture and hijacks an enhancer by three-dimensional genome structure remodeling in cervical cancer |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Revised 05.07.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a Integration of human papillomavirus (HPV) DNA into the human genome is a reputed key driver of cervical cancer. However, the effects of HPV integration on chromatin structural organization and gene expression are largely unknown. We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19. We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome, RNA, chromatin immunoprecipitation and high-throughput chromosome conformation capture (Hi-C) sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis. Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities, with correlation found between three-dimensional (3D) structural change and gene expression. Importantly, HPV integration divided one topologically associated domain (TAD) into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106, with a decrease in PEG3 expression and an increase in CCDC106 expression. This expression dysregulation was further confirmed using 10 samples from our cohort, which exhibited the same HPV-CCDC106 integration. In summary, we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling. Thus, this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cervical cancer | |
| 650 | 4 | |a Enhancer | |
| 650 | 4 | |a Fusion gene | |
| 650 | 4 | |a HPV integration | |
| 650 | 4 | |a Hi-C | |
| 650 | 4 | |a TAD | |
| 650 | 7 | |a CCDC106 protein, human |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Chromatin |2 NLM | |
| 650 | 7 | |a Kruppel-Like Transcription Factors |2 NLM | |
| 650 | 7 | |a PEG3 protein, human |2 NLM | |
| 700 | 1 | |a Hong, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Da |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Liming |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Bei |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Ci |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Yifan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhi, Wenhua |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Ruidi |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Juncheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Wencheng |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Xun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qinghua |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qinglei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Kezhen |e verfasserin |4 aut | |
| 700 | 1 | |a Sung, Wing-Kin |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guoliang |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Peng |e verfasserin |4 aut | |
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