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Title: NOVEL DNA BINDING SPECIFICITIES OF A PUTATIVE MAREK'S DISEASE VIRUS BZIP ONCOPROTEIN, MEQ

Author
item QIAN, ZHENG - CASE WESTERN RESERVE
item BRUNOVSKIS, PETER - CASE WESTERN RESERVE
item Lee, Lucy
item KUNG, HSING-JIEN - CASE WESTERN RESERVE

Submitted to: International Marek's Disease Symposium Abstracts and Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 9/7/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Marek's disease virus (MDV) is a highly oncogenic herpesvirus that can cause T-lymphomas and peripheral nerve demyelination in chickens. Meq, a candidate oncogene of MDV, encodes a basic leucine-zipper (bZIP) transcription factor which dimerizes with itself and c-Jun and has a C-terminal proline-rich domain with potent transactivation activity. Using a PCR-based CASTing (cyclic amplification of selected targets) approach, we have determined the optimal bindings sites for Meq/Jun heterodimers and the Meq/Meq homodimers. Meq/Jun heterodimers were found to optimally bind CRE/TRE consensus sequences. This is consistent with our previous functional analysis implicating Meq/Jun heterodimers in the transactivation of the Meq promoter through a CRE/TRE-like sequence. Interestingly, Meq/Meq homodimers were found to bind two distinct motif elements. The first (GAGTGATGAC(G)TCATC) consensus has a TRE/CRE core flanked by additional nucleotides, similar to the binding motif of Maf, another bZIP oncoprotein. Methylation interference and mutational analyses confirmed the importance of the flanking residues. The second Meq binding site (PuACACACAPy) bears a different consensus not shared by other bZIP proteins. In addition to this consensus sequence, binding to this element 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. Since such a site can be found around the MDV origin of replication, our results provide a baseline for the identification of not only Meq-responsive targets, but also its possible role in viral replication.