The Herpes Simplex Virus 1 Protein ICP4 Acts as both an Activator and a Repressor of Host Genome Transcription during Infection
- 1 October 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 41 (10), MCB0017121
- https://doi.org/10.1128/mcb.00171-21
Abstract
Infection by herpes simplex virus 1 (HSV-1) impacts nearly all steps of host cell gene expression. The regulatory mechanisms by which this occurs, and the interplay between host and viral factors, have yet to be fully elucidated. We investigated how the occupancy of RNA polymerase II (Pol II) on the host genome changes during HSV-1 infection and is impacted by the viral immediate early protein ICP4. Pol II ChIP-seq experiments revealed ICP4-dependent decreases and increases in Pol II levels across the bodies of hundreds of genes. Our data suggest ICP4 represses host transcription by inhibiting recruitment of Pol II and activates host genes by promoting release of Pol II from promoter proximal pausing into productive elongation. Consistent with this, ICP4 was required for the decrease in levels of the pausing factor NELF-A on several HSV-1 activated genes after infection. In the absence of infection, exogenous expression of ICP4 activated, but did not repress, transcription of some genes in a chromatin-dependent context. Our data support the model that ICP4 decreases promoter proximal pausing on host genes activated by infection, and ICP4 is necessary, but not sufficient, to repress transcription of host genes during viral infection.Keywords
Funding Information
- HHS | NIH | National Institute of General Medical Sciences (T32 GM008759)
- HHS | NIH | National Institute of General Medical Sciences (F31 GM125366)
- HHS | NIH | National Institute of General Medical Sciences (R01 GM068414)
This publication has 66 references indexed in Scilit:
- Defining the Status of RNA Polymerase at PromotersCell Reports, 2012
- Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoansNature Reviews Genetics, 2012
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- BEDTools: a flexible suite of utilities for comparing genomic featuresBioinformatics, 2010
- Progression through the RNA Polymerase II CTD CycleMolecular Cell, 2009
- rtracklayer: an R package for interfacing with genome browsersBioinformatics, 2009
- MEME SUITE: tools for motif discovery and searchingNucleic Acids Research, 2009
- Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene listsNucleic Acids Research, 2008
- Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promotersGene, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005