EMPLOYING GENOMICS, EPIGENETICS, AND IMMUNOGENETICS TO CONTROL DISEASES INDUCED BY AVIAN TUMOR VIRUSES
Location: Avian Disease and Oncology Laboratory
Title: Marek's Disease Virus Infection Induces Widespread Differential Chromatin Marks in Inbred Chicken Lines
| Mitra, Apratim - |
| Luo, Juan - |
| Zhao, Keji - |
| Song, Jiuzhou - |
Submitted to: Plant and Animal Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: November 30, 2012
Publication Date: January 14, 2013
Citation: Mitra, A., Luo, J., Zhang, H., Zhao, K., Song, J. 2013. Marek's Disease Virus Infection Induces Widespread Differential Chromatin Marks in Inbred Chicken Lines [abstract]. Plant and Animal Genome XXI Conference, January 12-16, 2013, San Diego, California. A-P0650. Available:https://pag.confex.com/pag/xxi/webprogram/Paper5688.html.
Marek’s disease (MD) is a neoplastic disease in chickens caused by the MD virus (MDV). Successful vaccine development against MD has resulted in increased virulence of MDV and the understanding of genetic resistance to the disease is, therefore, crucial to long-term control strategies. Also, epigenetic factors are believed to be one of the major determinants of disease response. Here, we carried out comprehensive analyses of the epigenetic landscape induced by MDV, utilizing genome-wide histone H3 lysine 4 and lysine 27 trimethylation maps from chicken lines with varying resistance to MD. Differential chromatin marks were observed on genes previously implicated in the disease such as MX1 and CTLA-4 and also on genes reported in other cancers including IGF2BP1 and GAL. We detected bivalent domains on immune-related transcriptional regulators BCL6, CITED2 and EGR1, which underwent dynamic changes in both lines as a result of MDV infection. In addition, putative roles for GAL in the mechanism of MD progression were revealed. Our results confirm the presence of widespread epigenetic differences induced by MD in chicken lines with different levels of genetic resistance. A majority of observed epigenetic changes were indicative of increased levels of viral infection in the susceptible line symptomatic of lowered immunocompetence in these birds caused by early cytolytic infection. The GAL system that has known anti-proliferative effects in other cancers is also revealed to be potentially involved in MD progression. Our study provides further insight into the mechanisms of MD progression while revealing a complex landscape of epigenetic regulatory mechanisms that varies depending on host factors.