Characterization of the DNA-binding properties of herpes simplex virus regulatory protein ICP4

Kattar-Cooley, Patricia A.; Wilcox, Kent W.

doi:10.1128/jvi.63.2.696-704.1989

Cited by 49 publications

(43 citation statements)

References 50 publications

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“…1 a shows interphase and mitotic HeLa cells, fixed and stained with the DNA stain DAPI and an antibody that recognizes the viral immediate-early protein ICP4. ICP4 binds to viral DNA and is the main transcriptional activator protein encoded by HSV-1 (Kattar-Cooley and Wilcox 1989; Smiley et al 1991; Allen and Everett 1997). Viral replication compartments were present in both interphase and mitotic infected cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation

Spencer

Kruhlak

Jenkins

et al. 2000

The Journal of Cell Biology

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All nuclear RNA synthesis is repressed during the mitotic phase of the cell cycle. In addition, RNA polymerase II (RNAP II), nascent RNA and many transcription factors disengage from DNA during mitosis. It has been proposed that mitotic transcription repression and disengagement of factors are due to either mitotic chromatin condensation or biochemical modifications to the transcription machinery. In this study, we investigate the requirement for chromatin condensation in establishing mitotic transcription repression and factor loss, by analyzing transcription and RNAP II localization in mitotic cells infected with herpes simplex virus type 1. We find that virus-infected cells enter mitosis and that mitotic viral DNA is maintained in a nucleosome-free and noncondensed state. Our data show that RNAP II transcription is repressed on cellular genes that are condensed into mitotic chromosomes and on viral genes that remain nucleosome free and noncondensed. Although RNAP II may interact indirectly with viral DNA during mitosis, it remains transcriptionally unengaged. This study demonstrates that mitotic repression of transcription and loss of transcription factors from mitotic DNA can occur independently of nucleosomal chromatin condensation.

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Section: Resultsmentioning

confidence: 99%

Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation

Spencer

Kruhlak

Jenkins

et al. 2000

The Journal of Cell Biology

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“…A proteinase K resistant domain of Vmwl75 binds to the IE-3 capsite Vmw175 in nuclear extracts binds specifically to DNA sequences which contain the consensus ATCGTC (23,39), including that at the capsite of the IE-3 promoter (25,32). Mutational analyses of the portions of Vmwl75 that are important for this binding have strongly suggested that conserved region 2 (12) is part of the DNA binding domain (16,32,33) but the involvement of other portions of the protein could not be excluded (8,32).…”

Section: Resultsmentioning

confidence: 99%

The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain

Everett¹,

Paterson²,

Elliott³

1990

Nucleic Acids Research

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Herpes simplex virus type 1 expresses five immediate-early (IE) polypeptides. In the absence of functional Vmw175 (the product of IE gene 3) activation of transcription of later classes of viral genes and repression of IE gene expression does not occur. The recognition of specific DNA sequences by Vmw175 requires, as determined by sensitivity to mutation, a part of the protein highly conserved in the corresponding proteins of related herpes viruses. However, mutations in other parts of the protein can also disrupt specific DNA binding. This paper shows that the DNA binding domain of Vmw175 can be liberated as a functional unit by digestion with proteinase K. Analysis of mutant Vmw175 proteins showed that the proteinase K resistant domain has an amino terminus between amino acid residues 229 and 292, while its carboxy terminus is between residues 495 and 518. Mutations outside this region which affect DNA binding by the intact protein do not eliminate binding of the proteinase K resistant domain. This implies that direct DNA binding by Vmw175 involves a linear subsection of the polypeptide, and that mutations in other parts of the polypeptide which affect DNA binding of the whole protein do so by indirect means.

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“…Purification of ICP4 Fraction IX of affinity DNA-cellulose purified ICP4 (>90% of the total protein mass) was used in our assays (Kattar-Cooley and Wilcox, 1989).…”

Section: Methodsmentioning

confidence: 99%

The interaction of ICP4 with cell/infected-cell factors and its state of phosphorylation modulate differential recognition of leader sequences in herpes simplex virus DNA.

1991

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Regulation of herpes simplex virus (HSV) gene expression requires the synthesis of functional ICP4, a phosphoprotein that binds to several specific sites in virus DNA and acts in trans either to activate or to repress transcription of the three major kinetic classes of virus genes. Binding of ICP4 to specific sites in alpha genes (which are the first to be transcribed) causes repression of alpha‐gene expression. ICP4 also indirectly participates in the formation of DNA‐protein complexes with sequences present in the promoter/regulatory and leader regions of the beta and gamma genes that are sequentially activated later in infection. Here we demonstrate that the extent of phosphorylation of ICP4 contributes to its ability to participate differentially in complex formation with cis‐acting elements present in beta and gamma genes. Dephosphorylated ICP4 retains its binding properties for the high affinity sites present in alpha promoters, whereas only phosphorylated forms of the protein are able to participate in complex formation with model beta and gamma sequences. These studies also reveal a requirement for cell and infected‐cell factors to recognize the beta and gamma sequences. Our data suggest that the state of phosphorylation and concentration of ICP4 within the nucleus of infected cells determine the extent to which ICP4 interacts with these other factors.

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Characterization of the DNA-binding properties of herpes simplex virus regulatory protein ICP4

Cited by 49 publications

References 50 publications

Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation

Mitotic Transcription Repression in Vivo in the Absence of Nucleosomal Chromatin Condensation

The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain

The interaction of ICP4 with cell/infected-cell factors and its state of phosphorylation modulate differential recognition of leader sequences in herpes simplex virus DNA.

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