Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication

ABSTRACT Elongins B and C are members of complexes that increase the efficiency of transcriptional elongation by RNA polymerase II (RNAPII) and enhance the monoubiquitination of histone H2B, an epigenetic mark of actively transcribed genes. Here we show that, in addition to its role in facilitating...

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Autores principales:	Jiwon Hwang, Ryan T. Saffert, Robert F. Kalejta
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f40ccdd11f904dafb4531c88bda7b46b
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spelling	oai:doaj.org-article:f40ccdd11f904dafb4531c88bda7b46b2021-11-15T15:39:07ZElongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication10.1128/mBio.00023-112150-7511https://doaj.org/article/f40ccdd11f904dafb4531c88bda7b46b2011-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00023-11https://doaj.org/toc/2150-7511ABSTRACT Elongins B and C are members of complexes that increase the efficiency of transcriptional elongation by RNA polymerase II (RNAPII) and enhance the monoubiquitination of histone H2B, an epigenetic mark of actively transcribed genes. Here we show that, in addition to its role in facilitating transcription of the cellular genome, elongin B also enhances gene expression from the double-stranded DNA genome of human cytomegalovirus (HCMV), a pathogenic herpesvirus. Reducing the level of elongin B by small interfering RNA- or short hairpin RNA-mediated knockdown decreased viral mRNA expression, viral protein accumulation, viral DNA replication, and infectious virion production. Chromatin immunoprecipitation analysis indicated viral genome occupancy of the elongating form of RNAPII, and monoubiquitinated histone H2B was reduced in elongin B-deficient cells. These data suggest that, in addition to the previously documented epigenetic regulation of transcriptional initiation, HCMV also subverts cellular elongin B-mediated epigenetic mechanisms for enhancing transcriptional elongation to enhance viral gene expression and virus replication. IMPORTANCE The genetic and epigenetic control of transcription initiation at both cellular and viral promoters is well documented. Recently, the epigenetic modification of histone H2B monoubiquitination throughout the bodies of cellular genes has been shown to enhance the elongation of RNA polymerase II-initiated transcripts. Mechanisms that might control the elongation of viral transcripts are less well studied. Here we show that, as with cellular genes, elongin B-mediated monoubiquitination of histone H2B also facilitates the transcriptional elongation of human cytomegalovirus genes. This and perhaps other epigenetic markings of actively transcribed regions may help in identifying viral genes expressed during in vitro latency or during natural infections of humans. Furthermore, this work identifies a novel, tractable model system to further study the regulation of transcriptional elongation in living cells.Jiwon HwangRyan T. SaffertRobert F. KalejtaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 2 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jiwon Hwang Ryan T. Saffert Robert F. Kalejta Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication
description	ABSTRACT Elongins B and C are members of complexes that increase the efficiency of transcriptional elongation by RNA polymerase II (RNAPII) and enhance the monoubiquitination of histone H2B, an epigenetic mark of actively transcribed genes. Here we show that, in addition to its role in facilitating transcription of the cellular genome, elongin B also enhances gene expression from the double-stranded DNA genome of human cytomegalovirus (HCMV), a pathogenic herpesvirus. Reducing the level of elongin B by small interfering RNA- or short hairpin RNA-mediated knockdown decreased viral mRNA expression, viral protein accumulation, viral DNA replication, and infectious virion production. Chromatin immunoprecipitation analysis indicated viral genome occupancy of the elongating form of RNAPII, and monoubiquitinated histone H2B was reduced in elongin B-deficient cells. These data suggest that, in addition to the previously documented epigenetic regulation of transcriptional initiation, HCMV also subverts cellular elongin B-mediated epigenetic mechanisms for enhancing transcriptional elongation to enhance viral gene expression and virus replication. IMPORTANCE The genetic and epigenetic control of transcription initiation at both cellular and viral promoters is well documented. Recently, the epigenetic modification of histone H2B monoubiquitination throughout the bodies of cellular genes has been shown to enhance the elongation of RNA polymerase II-initiated transcripts. Mechanisms that might control the elongation of viral transcripts are less well studied. Here we show that, as with cellular genes, elongin B-mediated monoubiquitination of histone H2B also facilitates the transcriptional elongation of human cytomegalovirus genes. This and perhaps other epigenetic markings of actively transcribed regions may help in identifying viral genes expressed during in vitro latency or during natural infections of humans. Furthermore, this work identifies a novel, tractable model system to further study the regulation of transcriptional elongation in living cells.
format	article
author	Jiwon Hwang Ryan T. Saffert Robert F. Kalejta
author_facet	Jiwon Hwang Ryan T. Saffert Robert F. Kalejta
author_sort	Jiwon Hwang
title	Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication
title_short	Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication
title_full	Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication
title_fullStr	Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication
title_full_unstemmed	Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication
title_sort	elongin b-mediated epigenetic alteration of viral chromatin correlates with efficient human cytomegalovirus gene expression and replication
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/f40ccdd11f904dafb4531c88bda7b46b
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Elongin B-Mediated Epigenetic Alteration of Viral Chromatin Correlates with Efficient Human Cytomegalovirus Gene Expression and Replication

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