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3D landscape of Hepatitis B virus interactions with human chromatins

Hepatitis B viral (HBV) DNAs, including covalently closed circular DNA (cccDNA) and integrated HBV DNA forms, are considered to be primary contributors to the development and progression of HBV-associated liver diseases. However, it remains largely unclear how HBV DNAs communicate with human chromat...

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Autores principales: Yang, Bo, Li, Boyuan, Jia, Liyang, Jiang, Yongpeng, Wang, Xin, Jiang, Shaodong, Du, Shunda, Ji, Xiong, Yang, Pengyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Singapore 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769987/
https://www.ncbi.nlm.nih.gov/pubmed/33372176
http://dx.doi.org/10.1038/s41421-020-00218-1
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author Yang, Bo
Li, Boyuan
Jia, Liyang
Jiang, Yongpeng
Wang, Xin
Jiang, Shaodong
Du, Shunda
Ji, Xiong
Yang, Pengyuan
author_facet Yang, Bo
Li, Boyuan
Jia, Liyang
Jiang, Yongpeng
Wang, Xin
Jiang, Shaodong
Du, Shunda
Ji, Xiong
Yang, Pengyuan
author_sort Yang, Bo
collection PubMed
description Hepatitis B viral (HBV) DNAs, including covalently closed circular DNA (cccDNA) and integrated HBV DNA forms, are considered to be primary contributors to the development and progression of HBV-associated liver diseases. However, it remains largely unclear how HBV DNAs communicate with human chromatin. Here we employed a highly sensitive technology, 3C-high-throughput genome-wide translocation sequencing (3C-HTGTS), to globally identify HBV DNA–host DNA contacts in cellular models of HBV infection. HBV DNA does not randomly position in host genome but instead preferentially establishes contacts with the host DNA at active chromatin regions. HBV DNA–host DNA contacts are significantly enriched at H3K4me1-marked regions modified by KMT2C/D; this histone modification is also observed in the HBV cccDNA mini-chromosome and strongly influences HBV transcription. On the other hand, chromatin loop formed by integrated HBV DNA with host genomic DNA was found in transcriptionally active regions. Furthermore, HBV infection influences host gene expression accompanied with HBV DNA–host DNA contacts. Our study provides a 3D landscape of spatial organization of cccDNA and integrated HBV DNA within the human genome, which lays the foundation for a better understanding of the mechanisms how HBV involves in liver disease development and progression.
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spelling pubmed-77699872021-01-07 3D landscape of Hepatitis B virus interactions with human chromatins Yang, Bo Li, Boyuan Jia, Liyang Jiang, Yongpeng Wang, Xin Jiang, Shaodong Du, Shunda Ji, Xiong Yang, Pengyuan Cell Discov Article Hepatitis B viral (HBV) DNAs, including covalently closed circular DNA (cccDNA) and integrated HBV DNA forms, are considered to be primary contributors to the development and progression of HBV-associated liver diseases. However, it remains largely unclear how HBV DNAs communicate with human chromatin. Here we employed a highly sensitive technology, 3C-high-throughput genome-wide translocation sequencing (3C-HTGTS), to globally identify HBV DNA–host DNA contacts in cellular models of HBV infection. HBV DNA does not randomly position in host genome but instead preferentially establishes contacts with the host DNA at active chromatin regions. HBV DNA–host DNA contacts are significantly enriched at H3K4me1-marked regions modified by KMT2C/D; this histone modification is also observed in the HBV cccDNA mini-chromosome and strongly influences HBV transcription. On the other hand, chromatin loop formed by integrated HBV DNA with host genomic DNA was found in transcriptionally active regions. Furthermore, HBV infection influences host gene expression accompanied with HBV DNA–host DNA contacts. Our study provides a 3D landscape of spatial organization of cccDNA and integrated HBV DNA within the human genome, which lays the foundation for a better understanding of the mechanisms how HBV involves in liver disease development and progression. Springer Singapore 2020-12-29 /pmc/articles/PMC7769987/ /pubmed/33372176 http://dx.doi.org/10.1038/s41421-020-00218-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yang, Bo
Li, Boyuan
Jia, Liyang
Jiang, Yongpeng
Wang, Xin
Jiang, Shaodong
Du, Shunda
Ji, Xiong
Yang, Pengyuan
3D landscape of Hepatitis B virus interactions with human chromatins
title 3D landscape of Hepatitis B virus interactions with human chromatins
title_full 3D landscape of Hepatitis B virus interactions with human chromatins
title_fullStr 3D landscape of Hepatitis B virus interactions with human chromatins
title_full_unstemmed 3D landscape of Hepatitis B virus interactions with human chromatins
title_short 3D landscape of Hepatitis B virus interactions with human chromatins
title_sort 3d landscape of hepatitis b virus interactions with human chromatins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769987/
https://www.ncbi.nlm.nih.gov/pubmed/33372176
http://dx.doi.org/10.1038/s41421-020-00218-1
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