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RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation

Gammaherpesviruses have a common biological characteristic, latency and lytic replication. The balance between these two phases in murine gammaherpesvirus 68 (MHV-68) is controlled by the replication and transcription activator (RTA) gene. In this report, we investigated the effect of DNA demethylat...

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Autores principales: Yang, Zhangsheng, Tang, Haidong, Huang, Hai, Deng, Hongyu
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644783/
https://www.ncbi.nlm.nih.gov/pubmed/19234612
http://dx.doi.org/10.1371/journal.pone.0004556
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author Yang, Zhangsheng
Tang, Haidong
Huang, Hai
Deng, Hongyu
author_facet Yang, Zhangsheng
Tang, Haidong
Huang, Hai
Deng, Hongyu
author_sort Yang, Zhangsheng
collection PubMed
description Gammaherpesviruses have a common biological characteristic, latency and lytic replication. The balance between these two phases in murine gammaherpesvirus 68 (MHV-68) is controlled by the replication and transcription activator (RTA) gene. In this report, we investigated the effect of DNA demethylation and histone acetylation on MHV-68 replication. We showed that distinctive methylation patterns were associated with MHV-68 at the RTA promoter during latency or lytic replication. Treatment of MHV-68 latently-infected S11E cells with a DNA methyltransferases (DNMTs) inhibitor 5-azacytidine (5-AzaC), only weakly reactivated MHV-68, despite resulted in demethylation of the viral RTA promoter. In contrast, treatment with a histone deacetylase (HDAC) inhibitor trichostatin A (TSA) strongly reactivated MHV-68 from latency, and this was associated with significant change in histone H3 and H4 acetylation levels at the RTA promoter. We further showed that HDAC3 was recruited to the RTA promoter and inhibited RTA transcription during viral latency. However, TSA treatment caused rapid removal of HDAC3 and also induced passive demethylation at the RTA promoter. In vivo, we found that the RTA promoter was hypomethylated during lytic infection in the lung and that methylation level increased with virus latent infection in the spleen. Collectively, our data showed that histone acetylation, but not DNA demethylation, is sufficient for effective reactivation of MHV-68 from latency in S11E cells.
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spelling pubmed-26447832009-02-23 RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation Yang, Zhangsheng Tang, Haidong Huang, Hai Deng, Hongyu PLoS One Research Article Gammaherpesviruses have a common biological characteristic, latency and lytic replication. The balance between these two phases in murine gammaherpesvirus 68 (MHV-68) is controlled by the replication and transcription activator (RTA) gene. In this report, we investigated the effect of DNA demethylation and histone acetylation on MHV-68 replication. We showed that distinctive methylation patterns were associated with MHV-68 at the RTA promoter during latency or lytic replication. Treatment of MHV-68 latently-infected S11E cells with a DNA methyltransferases (DNMTs) inhibitor 5-azacytidine (5-AzaC), only weakly reactivated MHV-68, despite resulted in demethylation of the viral RTA promoter. In contrast, treatment with a histone deacetylase (HDAC) inhibitor trichostatin A (TSA) strongly reactivated MHV-68 from latency, and this was associated with significant change in histone H3 and H4 acetylation levels at the RTA promoter. We further showed that HDAC3 was recruited to the RTA promoter and inhibited RTA transcription during viral latency. However, TSA treatment caused rapid removal of HDAC3 and also induced passive demethylation at the RTA promoter. In vivo, we found that the RTA promoter was hypomethylated during lytic infection in the lung and that methylation level increased with virus latent infection in the spleen. Collectively, our data showed that histone acetylation, but not DNA demethylation, is sufficient for effective reactivation of MHV-68 from latency in S11E cells. Public Library of Science 2009-02-23 /pmc/articles/PMC2644783/ /pubmed/19234612 http://dx.doi.org/10.1371/journal.pone.0004556 Text en Yang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yang, Zhangsheng
Tang, Haidong
Huang, Hai
Deng, Hongyu
RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation
title RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation
title_full RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation
title_fullStr RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation
title_full_unstemmed RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation
title_short RTA Promoter Demethylation and Histone Acetylation Regulation of Murine Gammaherpesvirus 68 Reactivation
title_sort rta promoter demethylation and histone acetylation regulation of murine gammaherpesvirus 68 reactivation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644783/
https://www.ncbi.nlm.nih.gov/pubmed/19234612
http://dx.doi.org/10.1371/journal.pone.0004556
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