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Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10835-40. Epub 2007 Jun 19.

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

Author information

1
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4-131, 4 Center Drive, Bethesda, MD 20892, USA.

Abstract

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.

PMID:
17578910
PMCID:
PMC1894567
DOI:
10.1073/pnas.0704351104
[Indexed for MEDLINE]
Free PMC Article

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