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Open Access Research article

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

Apratim Mitra1, Juan Luo1, Huanming Zhang2, Kairong Cui3, Keji Zhao3 and Jiuzhou Song1*

  • * Corresponding author: Jiuzhou Song songj88@umd.edu

  • † Equal contributors

Author Affiliations

1 Department of Animal & Avian Sciences, University of Maryland, College Park, MD, USA

2 USDA, ARS, Avian Disease and Oncology Laboratory, East Lansing, MI, USA

3 Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

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BMC Genomics 2012, 13:557  doi:10.1186/1471-2164-13-557

Published: 16 October 2012

Abstract

Background

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.

Results

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.

Conclusion

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.

Keywords:
Histone modifications; Thymus; Differential marks; Bivalent domain; Chromatin signature; Marek’s disease