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Title: Genome-wide identification of host genes directly regulated by Marek's disease virus (MDV) oncoprotein Meq

Author
item SUBRAMANIAM, SUGA - Michigan State University
item BROWN, C - Michigan State University
item NIIKURA, MASAHIRO - Simon Fraser University
item Cheng, Hans

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/6/2011
Publication Date: 7/20/2011
Citation: Subramaniam, S., Brown, C.T., Niikura, M., Cheng, H.H. 2011. Genome-wide identification of host genes directly regulated by Marek's disease virus (MDV) oncoprotein Meq [abstract]. American Society for Virology 30th Annual Meeting Scientific Program and Abstracts, University of Minnesota, July 16-20, 2011. P8-3 p. 273.

Interpretive Summary:

Technical Abstract: Marek's disease (MD) is a contagious lymphoproliferative and neurotropic disease of poultry caused by the Marek's disease virus (MDV), an oncogenic alphaherpesvirus. Despite the use of vaccines, field strains of MDV continue to evolve resulting in unpredictable disease outbreaks. Therefore, understanding the molecular basis for oncogenesis is of both fundamental and agricultural importance. MDV oncogenicity is largely attributed to the bZIP transcription factor Meq, which homodimerizes and heterodimerizes with c-Jun and other bZIP proteins. Our major objective is to gain a comprehensive understanding of host genes and proteins directly regulated by Meq. We used an immortalized chicken embryo fibroblast cell line (DF-1) transfected with Meq as our model. To identify genes directly regulated by Meq, DNA fractions bound by Meq or c-Jun were enriched by chromatin immunoprecipitation using anti-Meq and anti-c-Jun antibodies followed by massive parallel sequencing (ChIP-seq). The identified sites were widely distributed between 19,914 intergenic and 2,420 intragenic peaks with 1,832 genes within 2 kb. Motif analysis revealed novel and known Meq binding motifs. Pathway analysis indicated that Meq transforms the chicken cells via the c-Jun pathway as predicted previously. Our results from DNA microarrays showed 2,013 genes were differentially expressed (p<0.05) between DF-1 and DF-1-Meq. Integrating ChIP-seq and microarray datasets revealed 1,722 candidate genes involved in direct interactions of Meq with the chicken genome. These results are being further validated in vivo by using actual tumors from infected birds to gain higher confidence. Conclusion: This study is the first report providing a global view of all genes directly regulated by Meq in vitro. Furthermore, it has also shown that Meq not only imparts transforming potential through the Jun-pathway but also through multiple cellular metabolic pathways.