Location: Avian Disease and Oncology ResearchTitle: Identification of direct gene targets that the MDV oncoprotein Meq regulates via ChIP and expression analyses Author
|C. Titus, Brown|
Submitted to: Plant and Animal Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: 1/12/2013
Publication Date: 1/13/2013
Citation: Subramaniam, S., Preeyanon, L., C. Titus, B., Cheng, H.H. 2013. Identification of direct gene targets that the MDV oncoprotein Meq regulates via ChIP and expression analyses [abstract]. Plant and Animal Genome XXI Conference, January 12-16, 2013, San Diego, California. A-W638. Available: https://pag.confex.com/pag/xxi/webprogram/Paper5456.html. Interpretive Summary:
Technical Abstract: Genetic resistance to Marek’s disease (MD) is characterized by the lack of tumors or nerve enlargements following exposure to Marek’s disease virus (MDV), a highly-oncogenic alphaherpesvirus. MDV Meq is a bZIP transcription factor and the likely MDV oncogene suggesting that one pathway for resistance is the inability of Meq to regulate the transcription of specific genes in individuals resistant to MD, thereby, failing to initiate transformation. Therefore, it is of interest to define DNA-binding sites and the genes that are directly regulated by Meq. Querying DF1 (chicken cell line) stably transfected with Meq (DF1-Meq), ChIP seq analysis identified 15,576 and 8,545 sites for Meq and c-Jun, respectively, which are highly enriched for promoter regions. Motif analysis for the Meq-binding sites have confirmed existing motifs (AP-1 and MERE II) as well as identified new ones. In parallel, microarray analysis between DF1 and DF1-Meq cells reveal 1,829 (FDR=0.01) differentially expressed genes with 1,575 being down-regulated in the presence of Meq. Integrating ChIP seq and expression profiling revealed 354 and 93 candidate genes that are down- or up-regulated by the direct binding of Meq, respectively. Pathway analysis has suggested genes and molecular mechanisms for MDV-induced transformation including the MAPK signaling cascade pathway, which has been experimentally validated for cellular growth. This rich dataset is being used to query MD genetic resistance and allele-specific expression between MD resistance and susceptible birds.