The polycomb group protein Bmi1 binds to the herpes simplex virus 1 latent genome and maintains repressive histone marks during latency.
The mechanism by which herpes simplex virus 1 (HSV-1) establishes latency in sensory neurons is largely unknown. Recent studies indicate that epigenetic modifications of the chromatin associated with the latent genome may play a key role in the transcriptional control of lytic genes during latency. In this study, we found both constitutive and facultative types of heterochromatin to be present on the latent HSV-1 genome. Deposition of the facultative marks trimethyl H3K27 and histone variant macroH2A varied at different sites on the genome, whereas the constitutive marker trimethyl H3K9 did not. In addition, we show that in the absence of the latency-associated transcript (LAT), the latent genome shows a dramatic increase in trimethyl H3K27, suggesting that expression of the LAT during latency may act to promote an appropriate heterochromatic state that represses lytic genes but is still poised for reactivation. Due to the presence of the mark trimethyl H3K27, we examined whether Polycomb group proteins, which methylate H3K27, were present on the HSV-1 genome during latency. Our data indicate that Bmi1, a member of the Polycomb repressive complex 1 (PRC1) maintenance complex, associates with specific sites in the genome, with the highest level of enrichment at the LAT enhancer. To our knowledge, these are the first data demonstrating that a virus can repress its gene transcription to enter latency by exploiting the mechanism of Polycomb-mediated repression.
Kwiatkowski
Dacia L
DL
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, 32610-0266, USA.
Thompson
Hilary W
HW
Bloom
David C
DC
D000818:Animals; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency
C489421:Bmi1 protein, mouse; D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1