Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein

Zheng Qian, Peter Brunovskis, Lucy Lee, Peter K. Vogt, Hsing Jien Kung

Research output: Contribution to journalArticle

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Abstract

Marek's disease virus is a highly oncogenic herpesvirus that can cause T lymphomas and peripheral nerve demyelination in chickens. meq, a candidate oncogene of Marek's disease virus, encodes a basic leucine zipper (bZIP) transcription factor which contains a large proline-rich domain in its C terminus. On the basis of its bZIP structural homology, meq is perhaps the only member of the jun-fos gene family completely viral in origin. We previously showed that Meq's C-terminal domain has potent transactivation activity and that its bZIP domain can dimerize with itself and with c-Jun also. In an effort to identify viral and cellular targets of Meq, we have determined the optimal binding sites for Meq-Jun heterodimers and Meq-Meq homodimers. By a PCR-based approach using cyclic amplification of selected targets, Meq-Jun heterodimers were found to optimally bind tetradecanoylphorhol acetate response element (TRE) and cyclic AMP response element (CRE) consensus sequences. This result was consistent with the results of our previous functional analysis implicating Meq-Jun heterodimers in the transactivation of the Meq promoter through a TRE- or CRE-like sequence. Interestingly, Meq-Meq homodimers were found to bind two distinct motif elements. The first [GAGTGATG AC(G)TCATC] has a consensus which includes a TRE or CRE core flanked by additional nucleotides critical for tight binding. Methylation interference and mutational analyses confirmed the importance of the flanking residues. The sequences of a subset of TRE and CRE sites selected by Meq-Meq are closely related to the binding motif of Maf, another bZIP oncoprotein. The second putative Meq binding site (RACACACAY) bears a completely different consensus not shared by other bZIP proteins. Binding to this consensus sequence also requires secondary structure characteristics associated with DNA bending. CACA motifs are known to promote DNA curvature and function in a number of special biological processes. Our results lend further weight to the increasing importance of DNA bending in transcriptional regulation and provide a baseline for the identification of Meq-responsive targets.

Original languageEnglish
Pages (from-to)7161-7170
Number of pages10
JournalJournal of Virology
Volume70
Issue number10
Publication statusPublished - Oct 1 1996
Externally publishedYes

Fingerprint

Leucine Zippers
leucine zipper
response elements
Herpesviridae
Oncogene Proteins
Response Elements
DNA
cyclic AMP
Cyclic AMP
Acetates
acetates
Marek Disease
Mardivirus
consensus sequence
Consensus Sequence
transcriptional activation
Transcriptional Activation
binding sites
Binding Sites
Basic-Leucine Zipper Transcription Factors

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Qian, Z., Brunovskis, P., Lee, L., Vogt, P. K., & Kung, H. J. (1996). Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein. Journal of Virology, 70(10), 7161-7170.

Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein. / Qian, Zheng; Brunovskis, Peter; Lee, Lucy; Vogt, Peter K.; Kung, Hsing Jien.

In: Journal of Virology, Vol. 70, No. 10, 01.10.1996, p. 7161-7170.

Research output: Contribution to journalArticle

Qian, Z, Brunovskis, P, Lee, L, Vogt, PK & Kung, HJ 1996, 'Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein', Journal of Virology, vol. 70, no. 10, pp. 7161-7170.
Qian Z, Brunovskis P, Lee L, Vogt PK, Kung HJ. Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein. Journal of Virology. 1996 Oct 1;70(10):7161-7170.
Qian, Zheng ; Brunovskis, Peter ; Lee, Lucy ; Vogt, Peter K. ; Kung, Hsing Jien. / Novel DNA binding specificities of a putative herpesvirus bZIP oncoprotein. In: Journal of Virology. 1996 ; Vol. 70, No. 10. pp. 7161-7170.
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abstract = "Marek's disease virus is a highly oncogenic herpesvirus that can cause T lymphomas and peripheral nerve demyelination in chickens. meq, a candidate oncogene of Marek's disease virus, encodes a basic leucine zipper (bZIP) transcription factor which contains a large proline-rich domain in its C terminus. On the basis of its bZIP structural homology, meq is perhaps the only member of the jun-fos gene family completely viral in origin. We previously showed that Meq's C-terminal domain has potent transactivation activity and that its bZIP domain can dimerize with itself and with c-Jun also. In an effort to identify viral and cellular targets of Meq, we have determined the optimal binding sites for Meq-Jun heterodimers and Meq-Meq homodimers. By a PCR-based approach using cyclic amplification of selected targets, Meq-Jun heterodimers were found to optimally bind tetradecanoylphorhol acetate response element (TRE) and cyclic AMP response element (CRE) consensus sequences. This result was consistent with the results of our previous functional analysis implicating Meq-Jun heterodimers in the transactivation of the Meq promoter through a TRE- or CRE-like sequence. Interestingly, Meq-Meq homodimers were found to bind two distinct motif elements. The first [GAGTGATG AC(G)TCATC] has a consensus which includes a TRE or CRE core flanked by additional nucleotides critical for tight binding. Methylation interference and mutational analyses confirmed the importance of the flanking residues. The sequences of a subset of TRE and CRE sites selected by Meq-Meq are closely related to the binding motif of Maf, another bZIP oncoprotein. The second putative Meq binding site (RACACACAY) bears a completely different consensus not shared by other bZIP proteins. Binding to this consensus sequence also requires secondary structure characteristics associated with DNA bending. CACA motifs are known to promote DNA curvature and function in a number of special biological processes. Our results lend further weight to the increasing importance of DNA bending in transcriptional regulation and provide a baseline for the identification of Meq-responsive targets.",
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