Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes.
Expression of herpes simplex virus type 1 (HSV1) immediate early (IE) genes is activated by a polypeptide component of the mature virion termed viral protein 16 (VP16). Stimulation of IE expression by VP16 operates via two cis-regulatory sequences: TAATGARAT, and the purine-rich hexanucleotide sequence GCGGAA. VP16 does not bind directly to either of the IE cis-regulatory sequences. Rather, these elements appear to represent binding sites for host cell proteins. Herein, we report the purification of a host cell factor that binds to the GCGGAA motif. We show further that this factor is capable of binding in vitro to an oligomerized form of the hexanucleotide sequence GAAACG, which is common to a variety of virus- and interferon-inducible genes. The GAAACG repeats of interferon- and virus-inducible genes, and the GA-rich repeats of HSV1 IE genes confer similar functional properties when appended to the promoter of a heterologous gene. These observations raise the possibility that HSV1 may activate its IE genes in a manner that exploits one of the components used by mammalian cells to combat virus infection.
LaMarco
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KL
Howard Hughes Medical Institute, Carnegie Institution of Washington, Baltimore, Maryland 21210.
McKnight
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SL
D000818:Animals; D002467:Cell Nucleus / Q000032:analysis; D004268:DNA-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005814:Genes, Viral; D017874:Immediate-Early Proteins; D007370:Interferon Type I / Q000494:pharmacology; D051379:Mice; D010455:Peptides / Q000302:isolation & purification* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D018139:Simplexvirus / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000302:isolation & purification* / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*
D004268:DNA-Binding Proteins; C050678:IE1 protein, Human herpesvirus 1; D017874:Immediate-Early Proteins; D007370:Interferon Type I; D010455:Peptides; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins