The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein

Expression of the herpes simplex virus (HSV) immediate early (IE)genes is regulated by a multiprotein complex that is assembled on the TAATGARAT enhancer core element. The complex contains the cellular POU domain protein Oct-1, the viral transactivator VP16, and the cellular cofactor host cell factor 1. The current model suggests that the assembly depends on recognition of the core element by Oct-1. Here, HSV infection of Oct-1-deficient mouse embryonic fibroblast cells demonstrates that Oct-1 is critical for IE gene expression at low multiplicities of infection (moi). However, the protein is not essential for IE gene expression at high moi, indicating that VP16-mediated transcriptional induction through other IE regulatory elements is also important. This induction depends, at least in part, on the GA-binding protein binding elements that are present in each IE enhancer domain. Surprisingly, whereas the viral IE genes are expressed after high moi infection of Oct-1-deficient cells, the assembly of viral replication factories is severely impaired, revealing a second critical role for Oct-1 in HSV replication. The results have implications for both the HSV lytic and latency-reactivation cycles.

Section: T He Transcriptional Regulation Of the Immediate Early (Ie)mentioning

confidence: 99%

Section: T He Transcriptional Regulation Of the Immediate Early (Ie)mentioning

confidence: 99%

Herpes simplex virus infections are arrested in Oct-1-deficient cells

Nogueira

Wang

Tantin

et al. 2004

“…T he cellular transcriptional coactivator host cell factor-1 (HCF-1) was originally isolated as a component of the herpes simplex virus (HSV) immediate early (IE) gene enhanceosome complex containing the cellular POU domain protein Oct-1 and the viral transactivator VP16 (1)(2)(3)(4)(5)(6). The protein has been most thoroughly studied in this context where it mediates the VP16 transcriptional activation of the viral IE genes (7,8).…”

mentioning

confidence: 99%

The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection

Narayanan

Ruyechan

Kristie

2007

120

123

Originally identified as an essential component of the herpes simplex virus immediate early (IE) gene enhancer complex, the transcriptional coactivator host cell factor-1 (HCF-1) has been implicated in a broad range of cellular regulatory circuits. The protein mediates activation through multiple interactions with transcriptional activators, coactivators, and chromatin remodeling complexes. However, the mechanisms involved in HCF-1-dependent transcriptional stimulation were undefined. By using a minimal HCF-1-dependent promoter and a model activator, the varicella zoster IE62 protein, it was determined that HCF-1 was not required for the assembly of the RNAPII basal complex, which depended solely on IE62 in conjunction with the cellular factor Sp1. In contrast, HCF-1 was required for recruitment of the histone methyltransferases Set1 and MLL1 (mixed-lineage leukemia 1), leading to histone H3K4 trimethylation and transcriptional activation. Similarly, in a varicella zoster virus lytic infection, HCF-1, Set1, and MLL1 were recruited to the viral genomic IE promoter, suggesting an essential role for HCF-1 in chromatin modification and remodeling during initiation of lytic infection. The results indicate that one biological rationale for the incorporation of the viral IE activators in the viral particle is to recruit HCF-1/histone methyltransferase complexes and promote assembly of the viral IE gene promoters into transcriptionally active chromatin. These studies also contribute to the model whereby the induced nuclear transport of HCF-1 in sensory neurons may be critical to the reactivation of latent herpesviruses by promoting the activation of chromatin modifications.chromatin ͉ histone methyltransferase ͉ chromatin modifications ͉ Sp1 ͉ transcription T he cellular transcriptional coactivator host cell factor-1 (HCF-1) was originally isolated as a component of the herpes simplex virus (HSV) immediate early (IE) gene enhanceosome complex containing the cellular POU domain protein Oct-1 and the viral transactivator VP16 (1-6). The protein has been most thoroughly studied in this context where it mediates the VP16 transcriptional activation of the viral IE genes (7,8). In an analogous manner, HCF-1 also mediates the induction of the related varicella zoster virus (VZV) IE genes by the viral transactivators ORF10 and IE62 (8). The transcription of these ␣-herpesvirus genes is regulated by multiple mechanisms and factors via complex combinatorial enhancer-promoter domains. Strikingly, HCF-1 has been shown to be essential for IE gene expression, suggesting that it mediates a common rate-limiting step. Most intriguingly, both HSV and VZV establish latency in the neurons of sensory ganglia. In these cells, HCF-1 is uniquely sequestered in the cytoplasm of sensory neurons and is rapidly transported to the nucleus upon stimulation that results in viral reactivation (9). Therefore, whereas the protein is essential for viral lytic replication, it may also be a key component in the ␣-herpesvirus latency reactivation cycle.Sinc...

“…The C1 factor, a unique transcription factor, was identified as a required component of the herpes simplex virus (HSV) immediate early gene enhancer complex (18)(19)(20)(21)(22)(23)(24). A cellular protein, the factor functions as the coordinator of the enhancer assembly by direct interactions with the cellular POUhomeodomain protein Oct-1 (25) and the viral encoded transactivator ␣-trans-induction factor [␣TIF (VP16)] (24,26,27).…”

mentioning

confidence: 99%

“…1, the C1 factor is expressed as a 230-kDa precursor containing a series of unique 20-amino acid reiterations (23,33). Amino-terminal sequencing of the products isolated from mammalian cells demonstrated these repeats (VCSNPPCETHETGTTNTATT) and an additional sequence (102 cleavage site, SNMSSNQDPPPAASDQGEVE), located directly carboxyl terminal to the reiterations, are the sites of specific proteolytic processing that generates a family of aminoand carboxyl-terminal polypeptides ranging from 180 kDa to 102 kDa (33).…”

mentioning

confidence: 99%

Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): A potential role for proteolytic regulation of coactivator function

Vogel

Kristie

2000

Site-specific proteolysis is an important biological mechanism for the regulation of cellular processes such as gene expression, cell signaling, development, and apoptosis. In transcriptional regulation, specific proteolysis regulates the localization and activity of many regulatory factors. The C1 factor (HCF), a cellular transcription factor and coactivator, undergoes site-specific proteolytic processing at a series of unusual amino acid reiterations to generate a family of amino-and carboxyl-terminal polypeptides that remain tightly associated. Expression and purification of bacterially expressed domains of the C1 factor identifies an autocatalytic activity that is responsible for the specific cleavage of the reiterations. In addition, coexpression of the autocatalytic domain with a heterologous protein containing a target cleavage site demonstrates that the C1 protease may also function in trans.protease ͉ enhancer ͉ trans-cleavage ͉ transport