Expression of the immediate early genes of herpes simplex virus I requires the assembly of a multiprotein RNAPII enhancer complex consisting of several viral and cellular transcription factors. This assembly provides a model for the analysis of the components involved in the specific activation of gene expression. The present study focuses upon the characterization of the mammalian C1 factor; a protein complex which interacts with the viral transactivator and is required for the enhancer assembly. Analysis of isolated cDNAs encoding the C1 factor indicate that it is a novel family of proteins which are specifically proteolytically processed from a large precursor. These proteins are generated by site-specific cleavage within a reiterated amino acid sequence. As the processing and assembly of this factor influences its activity, genetic screens have been designed for the analysis of the cleavage sequences and the isolation of the specific protease from mammalian cells. These studies have resulted in the identification of a number of novel factors which interact with the reiterated sequences of the C1 factor. The development of specific antiseras have determined that although the C1 factor is ubiquitously expressed in most tissues, the protein is localized to specific subnuclear structures in certain cell types. In addition, C1 factor homologs and have been identified and isolated from other animal systems to allow for the genetic analysis of these factors. The continuing studies focus upon questions concerning the role of the C1 factor processing in the transcription of the herpes simplex virus genes, the specific transport/localization of the protein, and the development of animal systems for the analysis of the functions of the protein in viral and cellular functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000711-02
Application #
5200595
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Narayanan, Aarthi; Ruyechan, William T; Kristie, Thomas M (2007) The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection. Proc Natl Acad Sci U S A 104:10835-40
Vogel, Jodi L; Kristie, Thomas M (2006) Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors. Proc Natl Acad Sci U S A 103:6817-22
Narayanan, Aarthi; Nogueira, Mauricio L; Ruyechan, William T et al. (2005) Combinatorial transcription of herpes simplex virus and varicella zoster virus immediate early genes is strictly determined by the cellular coactivator HCF-1. J Biol Chem 280:1369-75
Nogueira, Mauricio L; Wang, Victoria E H; Tantin, Dean et al. (2004) Herpes simplex virus infections are arrested in Oct-1-deficient cells. Proc Natl Acad Sci U S A 101:1473-8
Khurana, Bharat; Kristie, Thomas M (2004) A protein sequestering system reveals control of cellular programs by the transcriptional coactivator HCF-1. J Biol Chem 279:33673-83
Vogel, J L; Kristie, T M (2000) Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): a potential role for proteolytic regulation of coactivator function. Proc Natl Acad Sci U S A 97:9425-30
Vogel, J L; Kristie, T M (2000) The novel coactivator C1 (HCF) coordinates multiprotein enhancer formation and mediates transcription activation by GABP. EMBO J 19:683-90
Kristie, T M; Vogel, J L; Sears, A E (1999) Nuclear localization of the C1 factor (host cell factor) in sensory neurons correlates with reactivation of herpes simplex virus from latency. Proc Natl Acad Sci U S A 96:1229-33