The Dynamics of HCF-1 Modulation of Herpes Simplex Virus Chromatin during Initiation of Infection

Vogel, Joseph P.; Kristie, Thomas M.

doi:10.3390/v5051272

Cited by 34 publications

(35 citation statements)

References 124 publications

(154 reference statements)

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“…HCF-1 then recruits a regulatory complex containing Set1/MLL1 KMT and LSD1/ JMJD HDM to the viral IE promoters [61,102,103,104,129,130]. JMJD and LSD1 HDMs act in sequence to remove H3K9me3, such that the SET1/MLL1 KMT can then methylate H3K4 [61,68,102,103,104].…”

Section: Resultsmentioning

confidence: 99%

Chromatin Dynamics during Lytic Infection with Herpes Simplex Virus 1

Conn

Schang

2013

Viruses

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Latent HSV-1 genomes are chromatinized with silencing marks. Since 2004, however, there has been an apparent inconsistency in the studies of the chromatinization of the HSV-1 genomes in lytically infected cells. Nuclease protection and chromatin immunoprecipitation assays suggested that the genomes were not regularly chromatinized, having only low histone occupancy. However, the chromatin modifications associated with transcribed and non-transcribed HSV-1 genes were those associated with active or repressed transcription, respectively. Moreover, the three critical HSV-1 transcriptional activators all had the capability to induce chromatin remodelling, and interacted with critical chromatin modifying enzymes. Depletion or overexpression of some, but not all, chromatin modifying proteins affected HSV-1 transcription, but often in unexpected manners. Since 2010, it has become clear that both cellular and HSV-1 chromatins are highly dynamic in infected cells. These dynamics reconcile the weak interactions between HSV-1 genomes and chromatin proteins, detected by nuclease protection and chromatin immunoprecipitation, with the proposed regulation of HSV-1 gene expression by chromatin, supported by the marks in the chromatin in the viral genomes and the abilities of the HSV-1 transcription activators to modulate chromatin. It also explains the sometimes unexpected results of interventions to modulate chromatin remodelling activities in infected cells.

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Section: Resultsmentioning

confidence: 99%

Chromatin Dynamics during Lytic Infection with Herpes Simplex Virus 1

Conn

Schang

2013

Viruses

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“…HSV IE gene promoter regulatory regions are designed to respond to multiple transcription factors and transcriptional coactivators that function cooperatively to drive high-level expression in a rapid manner (Fig. 2) (Knipe et al, 2013; Kristie et al, 2010; Vogel and Kristie, 2013). During lytic infection, the viral encoded IE activator VP16 is released from the tegument structure of the infecting virus and is recruited to viral IE enhancer elements by interaction with the cellular POU domain protein Oct-1.…”

Section: Activators and Coactivators Controlling Hsv Ie Gene Expressionmentioning

confidence: 99%

“…HCF-1 interacts with many of the transcription factors that bind the IE promoter regions and it is critical for the transcriptional potential of these factors (Kristie et al, 2010). In recent years, it has become clear that the protein is a component of or associated with multiple chromatin modulation complexes and functions mechanistically to couple DNA binding transcription factors to cellular chromatin modulation complexes (Knipe et al, 2013; Kristie et al, 2010; Narayanan et al, 2007; Vogel and Kristie, 2013; Wysocka et al, 2003). These complexes play a role in modulating the dynamic between heterochromatic suppression and euchromatic activation of the viral genome.…”

Section: Activators and Coactivators Controlling Hsv Ie Gene Expressionmentioning

confidence: 99%

Dynamic modulation of HSV chromatin drives initiation of infection and provides targets for epigenetic therapies

Kristie

2015

Virology

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Upon infection, the genomes of herpesviruses undergo a striking transition from a non-nucleosomal structure to a chromatin structure. The rapid assembly and modulation of nucleosomes during the initial stage of infection results in an overlay of complex regulation that requires interactions of a plethora of chromatin modulation components. For herpes simplex virus, the initial chromatin dynamic is dependent on viral and host cell transcription factors and coactivators that mediate the balance between heterochromatic suppression of the viral genome and the euchromatin transition that allows and promotes the expression of viral immediate early genes. Strikingly similar to lytic infection, in sensory neurons this dynamic transition between heterochromatin and euchromatin governs the establishment, maintenance, and reactivation from the latent state. Chromatin dynamics in both the lytic infection and latency-reactivation cycles provides opportunities to shift the balance using small molecule epigenetic modulators to suppress viral infection, shedding, and reactivation from latency.

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“…Oct-1, SP1, GABP) that assemble a potent transcription enhancer complex. A primary driver of IE expression is the cellular coactivator HCF-1 that is assembled into IE enhancer complexes via direct interactions with multiple transcription factors, including the viral IE activator, VP16 (Vogel and Kristie, 2013). HCF-1 plays a key role in modulating the chromatin assembled on the IE genes as part of a complex containing histone demethylases (JMJD2/KDM4 and LSD1/KDM1A) and histone H3K4 methyltransferases (SETD1A and MLL1/KMT2A).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency

Alfonso

Turner

Beltran

et al. 2017

Cell Host & Microbe

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Summary The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) genes enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the Super Elongation Complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs. Significantly, compounds that enhance the levels of SEC-P-TEFb also potently stimulated HSV reactivation from latency both in a sensory ganglia model system and in vivo. Thus, transcriptional elongation of HSV IE genes is a key limiting parameter governing both the initiation of HSV infection and reactivation of latent genomes.

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The Dynamics of HCF-1 Modulation of Herpes Simplex Virus Chromatin during Initiation of Infection

Cited by 34 publications

References 124 publications

Chromatin Dynamics during Lytic Infection with Herpes Simplex Virus 1

Chromatin Dynamics during Lytic Infection with Herpes Simplex Virus 1

Dynamic modulation of HSV chromatin drives initiation of infection and provides targets for epigenetic therapies

Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency

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