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Molecular and Cellular Biology, July 2001, p. 4700-4712, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4700-4712.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

DNA Recognition by the Herpes Simplex Virus Transactivator VP16: a Novel DNA-Binding Structure

Robert Babb,1,dagger C. Chris Huang,1,Dagger Deborah J. Aufiero,2 and Winship Herr2,*

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724,2 and Graduate Program in Genetics, State University of New York at Stony Brook, Stony Brook, New York 117941

Received 6 February 2001/Returned for modification 19 March 2001/Accepted 19 April 2001

Upon infection, the herpes simplex virus (HSV) transcriptional activator VP16 directs the formation of a multiprotein-DNA complex---the VP16-induced complex---with two cellular proteins, the host cell factor HCF-1 and the POU domain transcription factor Oct-1, on TAATGARAT-containing sequences found in the promoters of HSV immediate-early genes. HSV VP16 contains carboxy-terminal sequences important for transcriptional activation and a central conserved core that is important for VP16-induced complex assembly. On its own, VP16 displays little, if any, sequence-specific DNA-binding activity. We show here that, within the VP16-induced complex, however, the VP16 core has an important role in DNA binding. Mutation of basic residues on the surface of the VP16 core reveals a novel DNA-binding surface with essential residues which are conserved among VP16 orthologs. These results illuminate how, through association with DNA, VP16 is able to interpret cis-regulatory signals in the DNA to direct the assembly of a multiprotein-DNA transcriptional regulatory complex.


* Corresponding author. Mailing address: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. Phone: (516) 367-8401. Fax: (516) 367-8454. E-mail: herr{at}cshl.org.

dagger Present address: Novartis Institute for Biomedical Research, Summit, NJ 07901.

Dagger Present address: DoubleTwist.com, Philadelphia, PA 19104.


Molecular and Cellular Biology, July 2001, p. 4700-4712, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4700-4712.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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