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Title: Genome-wide Identification of Host Genes Directly and Indirectly Regulated by Marek's Disease Virus (MDV) Oncoprotein Meq

Author
item SUBRAMANIAM, SUGA - Michigan State University
item BROWN, C TITUS - Michigan State University
item Cheng, Hans

Submitted to: Herpesvirus International Workshop
Publication Type: Abstract Only
Publication Acceptance Date: 7/24/2010
Publication Date: 7/24/2010
Citation: Subramaniam, S., Brown, C.T., Cheng, H.H. 2010. Genome-wide identification of host genes directly and indirectly regulated by Marek's disease virus (MDV) oncoprotein Meq [abstract]. In: 35th Annual International Herpesvirus Workshop, July 24-29, 2010, Salt Lake City, Utah. Paper No. 7.26.

Interpretive Summary:

Technical Abstract: Marek’s disease virus (MDV), a naturally occurring, oncogenic, cell-associated alphaherpesvirus, is the causative agent for Marek's disease (MD), a chicken T-cell lymphoma. Despite the use of MD vaccines, field strains of MDV continue to evolve resulting in unpredictable and spontaneous disease outbreaks. Thus, 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, as well as heterodimerizes, with c-Jun and other bZIP proteins. Despite this knowledge, there is limited understanding on the mechanisms of Meq-induced oncogenicity. Our major objective is to gain a comprehensive understanding of host genes and proteins directly and indirectly regulated by Meq. Utilizing the MSB-1 T cell line, latent MDV was reactivated with the addition of bromodeoxyuridine (BudR). Meq expression was monitored 0, 24, 48, 96 hrs after reactivation and the levels of Meq and Meq homodimers significantly decreased over time (p<0.05). With this ability to regulate and synchronize MDV replication, the global view of all genes regulated by Meq in both latent and lytic phases was determined using Affymetrix chicken genome microarrays. To identify genes directly regulated by Meq, DNA fractions bound by Meq and/or c-Jun were enriched by chromatin immunoprecipitation (ChIP) using anti-Meq or anti-c-Jun antibody following by Next generation sequencing. Integrating data from microarray and ChIP-seq analysis will result in the genome -wide mapping of direct and indirect interactions of Meq with the chicken genome. Furthermore, this resulting information establishes a platform to identify novel positional candidate genes for MD resistance. The most current results will be presented.