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Abstract
Marek's disease (MD) is a lymphoproliferative disease in chicken induced by Marek's disease virus (MDV). Although studies have focused on the genetic differences between the resistant and susceptible chicken, less is known about the role of epigenetic factors in MD. In this study, genome-wide histone modifications in the non-MHC-associated resistant and susceptible chicken lines were examined. We found that tri-methylation at histone H3 Lys4 (H3K4me3) enrichment is positively correlated with the expression of protein coding genes as well as microRNA (miRNA) genes, whereas tri-methylation at histone H3 Lys27 (H3K27me3) exhibits a negative correlation. By identifying line-specific histone modifications in MDV infection, we found unique H3K4me3 islands in the resistant chicken activated genes, which are related to immune response and cell adhesion. Interestingly, we also found some miRNAs from unique H3K27me3 patterns in the susceptible chickens that targeted genes involved in 5-hydroxytryptamine (5-HT)-receptor and adrenergic receptor pathways. In conclusion, dynamic line-specific histone modifications in response to MDV infection suggested that intrinsic epigenetic mechanisms may play a role in MD-resistance and -susceptibility.
Highlights
Marek’s disease (MD) is a lymphoproliferative disease characterized by infiltration of proliferating lymphoid cells into many tissues, including peripheral nerves, skin, muscle, liver, spleen, heart, kidney, gonads and proventriculus [1]
We reported the first genome-wide histone modification maps of H3K4me3 and H3K27me3 in chicken spleen during the latent phase of Marek’s disease virus (MDV) infection by using MDresistant and -susceptible chickens
Spleen provides a suitable microenvironment for the MDV transformed CD4+ T cells to produce progressive MD in susceptible L72 chicken
Summary
Marek’s disease (MD) is a lymphoproliferative disease characterized by infiltration of proliferating lymphoid cells into many tissues, including peripheral nerves, skin, muscle, liver, spleen, heart, kidney, gonads and proventriculus [1]. The causative agent of MD is Marek’s disease virus (MDV) which is a cell-associated herpesvirus belonging to a subgroup of Alphaherpesviridae according to its genome organization [2,3]. This disease is a unique natural model for lymphomas that overexpress Hodgkin’s antigen (CD30) in humans [4]. There is an early cytolytic phase (2–7 days post-infection, dpi) primarily in B lymphocytes which results in lymphocytolysis and inflammation. Infected lymphocytes are transformed and proliferate profusely from 28 dpi onwards to form tumors in various tissues
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