Cargando…
HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA
The hepatitis B X protein (HBx) plays a role in the epigenetic regulation of hepatitis B virus (HBV) replication. This study investigated the effects of HBx mutations on HBV transcription and the recruitment of HBx, histone acetyl-transferase P300 and histone deacetylase 1 (HDAC1) to circularized HB...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972884/ https://www.ncbi.nlm.nih.gov/pubmed/31964944 http://dx.doi.org/10.1038/s41598-020-57637-z |
_version_ | 1783489929369616384 |
---|---|
author | Chong, Chun Kong Cheng, Ching Yan Serene Tsoi, Sin Yi Jasmine Huang, Fung-Yu Liu, Fen Fung, James Seto, Wai-Kay Lai, Keane K.-Y. Lai, Ching-Lung Yuen, Man-Fung Wong, Danny Ka-Ho |
author_facet | Chong, Chun Kong Cheng, Ching Yan Serene Tsoi, Sin Yi Jasmine Huang, Fung-Yu Liu, Fen Fung, James Seto, Wai-Kay Lai, Keane K.-Y. Lai, Ching-Lung Yuen, Man-Fung Wong, Danny Ka-Ho |
author_sort | Chong, Chun Kong |
collection | PubMed |
description | The hepatitis B X protein (HBx) plays a role in the epigenetic regulation of hepatitis B virus (HBV) replication. This study investigated the effects of HBx mutations on HBV transcription and the recruitment of HBx, histone acetyl-transferase P300 and histone deacetylase 1 (HDAC1) to circularized HBV DNA (which resembles covalently closed circular DNA [cccDNA]). Compared with wild type, majority of mutants had lower levels of intracellular HBV RNA (44–77% reduction) and secretory HBsAg (25–81% reduction), and 12 mutants had a reduction in intracellular encapsidated HBV DNA (33–64% reduction). Eight mutants with >70% reduction in HBV RNA and/or HBsAg were selected for chromatin immunoprecipitation analysis. Four HBx mutants with mutations in amino acid residues 55–60 and 121–126 had a lower degree of HBx-cccDNA association than wild type HBx (mean % input: 0.02–0.64% vs. 3.08% in wild type). A reduced association between cccDNA and P300 (mean % input: 0.69–1.81% vs. 3.48% in wild type) and an augmented association with HDAC1 (mean % input: 4.01–14.0% vs. 1.53% in wild type) were detected. HBx amino acid residues 55–60 and 121–126 may play an important role in HBV transcription regulation, via their impeded interaction with cccDNA and altered recruitment of histone modifying enzymes to cccDNA. |
format | Online Article Text |
id | pubmed-6972884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69728842020-01-27 HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA Chong, Chun Kong Cheng, Ching Yan Serene Tsoi, Sin Yi Jasmine Huang, Fung-Yu Liu, Fen Fung, James Seto, Wai-Kay Lai, Keane K.-Y. Lai, Ching-Lung Yuen, Man-Fung Wong, Danny Ka-Ho Sci Rep Article The hepatitis B X protein (HBx) plays a role in the epigenetic regulation of hepatitis B virus (HBV) replication. This study investigated the effects of HBx mutations on HBV transcription and the recruitment of HBx, histone acetyl-transferase P300 and histone deacetylase 1 (HDAC1) to circularized HBV DNA (which resembles covalently closed circular DNA [cccDNA]). Compared with wild type, majority of mutants had lower levels of intracellular HBV RNA (44–77% reduction) and secretory HBsAg (25–81% reduction), and 12 mutants had a reduction in intracellular encapsidated HBV DNA (33–64% reduction). Eight mutants with >70% reduction in HBV RNA and/or HBsAg were selected for chromatin immunoprecipitation analysis. Four HBx mutants with mutations in amino acid residues 55–60 and 121–126 had a lower degree of HBx-cccDNA association than wild type HBx (mean % input: 0.02–0.64% vs. 3.08% in wild type). A reduced association between cccDNA and P300 (mean % input: 0.69–1.81% vs. 3.48% in wild type) and an augmented association with HDAC1 (mean % input: 4.01–14.0% vs. 1.53% in wild type) were detected. HBx amino acid residues 55–60 and 121–126 may play an important role in HBV transcription regulation, via their impeded interaction with cccDNA and altered recruitment of histone modifying enzymes to cccDNA. Nature Publishing Group UK 2020-01-21 /pmc/articles/PMC6972884/ /pubmed/31964944 http://dx.doi.org/10.1038/s41598-020-57637-z 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 Chong, Chun Kong Cheng, Ching Yan Serene Tsoi, Sin Yi Jasmine Huang, Fung-Yu Liu, Fen Fung, James Seto, Wai-Kay Lai, Keane K.-Y. Lai, Ching-Lung Yuen, Man-Fung Wong, Danny Ka-Ho HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA |
title | HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA |
title_full | HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA |
title_fullStr | HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA |
title_full_unstemmed | HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA |
title_short | HBV X protein mutations affect HBV transcription and association of histone-modifying enzymes with covalently closed circular DNA |
title_sort | hbv x protein mutations affect hbv transcription and association of histone-modifying enzymes with covalently closed circular dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972884/ https://www.ncbi.nlm.nih.gov/pubmed/31964944 http://dx.doi.org/10.1038/s41598-020-57637-z |
work_keys_str_mv | AT chongchunkong hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT chengchingyanserene hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT tsoisinyijasmine hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT huangfungyu hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT liufen hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT fungjames hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT setowaikay hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT laikeaneky hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT laichinglung hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT yuenmanfung hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna AT wongdannykaho hbvxproteinmutationsaffecthbvtranscriptionandassociationofhistonemodifyingenzymeswithcovalentlyclosedcirculardna |