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Title: Marek’s disease virus infection induces widespread differential chromatin marks in inbred chicken lines

Author
item MITRA, APRATIM - University Of Maryland
item LUO, JUAN - University Of Maryland
item Zhang, Huanmin
item CUI, KAIRONG - National Institutes Of Health (NIH)
item ZHAO, KEJI - National Institutes Of Health (NIH)
item SONG, JIUZHOU - University Of Maryland

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/8/2012
Publication Date: 10/16/2012
Citation: Mitra, A., Luo, J., Zhang, H., Cui, K., Zhao, K., Song, J. 2012. Marek’s disease virus infection induces widespread differential chromatin marks in inbred chicken lines. Biomed Central (BMC) Genomics. 2012(13):557. Available: http://www.biomedcentral.com/1471-2164/13/557.

Interpretive Summary: Marek’s disease (MD), a virus induced cancerous disease of domestic chickens, causes the world poultry industry about $2 billion annually. Many kinds of cancer cells carry aberrant epigenetic modifications, a kind of heritable change not found in or due to DNA variation. This study was aimed to explore such epigenetic modifications induced by MD viruses in resistant and highly susceptible lines of chickens. Our data showed such modifications were induced in multiple host genes by MD virus infection but differed between the two lines of chickens. Those modifications subsequently affected gene functions. The findings of this study are of importance in understanding the host biological processes upon viral infection and in developing science-based strategies to prevent infectious diseases.

Technical Abstract: Marek's disease (MD) is a neoplastic disease in chickens caused by MD virus (MDV). Continuous vaccination against MD may have contributed to a progressive increase in the virulence of MDV, and therefore, the understanding of genetic resistance to MD is considered crucial to the long-term control of the disease. We tested the hypothesis that MDV infection induces changes in epigenetic status of genes in a host genetics-dependent manner. We generated genome-wide histone 3 lysine 4 (H3K4) and histone 3 lysine 27 (H3K27) trimethylation maps in thymus tissues from lines of chickens distinctly different in genetic resistance to MD. Differential chromatin marks were observed on several genes previously implicated in MD, such as MX1, MMP2 and CTLA-4, and also on additional genes including EAF2, IGF2BP1 and GAL. We detected bivalent chromatin domains on transcriptional regulators, BCL6, CITED2 and EGR1, which play important roles in immune response. Dynamic changes in these domains coupled with significant changes in gene expression were observed in response to MDV infection both in the resistant and the susceptible lines of chickens, which suggest MDV induced chromatin modifications are involved in regulation of gene expression, and subsequently in tumorigenesis and tumor development. Moreover, novel putative roles for GAL and CITED2 were determined, which contribute to MD progression. We also found tissue-specific effects of MDV infection in some genes including IL-15 and NOS2 that exhibited differential marks only in spleen. Our results suggest widespread epigenetic changes were induced by MDV infection. The extent of which is dependent of the level of host genetic resistance to MD. In addition, the GAL system is known of anti-proliferative effects in some cancers. Its implication in MD progression warrants further investigation.