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Epigenetics. 2013 Apr 1;8(4):431-44. doi: 10.4161/epi.24361. Epub 2013 Mar 28.

DNMT gene expression and methylome in Marek's disease resistant and susceptible chickens prior to and following infection by MDV.

Author information

  • 1Department of Animal & Avian Sciences; University of Maryland; College Park, MD USA.
  • 2Center for Pharmacogenomics; Department of Medicine; Washington University School of Medicine; St. Louis, MO USA.
  • 3USDA; ARS, Avian Disease and Oncology Laboratory; East Lansing, MI USA; Department of Animal Science; Michigan State University; East Lansing, MI USA.
  • 4Laboratory of Molecular Immunology; National Heart, Lung and Blood Institute; National Institutes of Health; Bethesda, MD USA.

Abstract

Marek's disease (MD) is characterized as a T cell lymphoma induced by a cell-associated α-herpesvirus, Marek's disease virus type 1 (MDV1). As with many viral infectious diseases, DNA methylation variations were observed in the progression of MD; these variations are thought to play an important role in host-virus interactions. We observed that DNA methyltransferase 3a (DNMT3a) and 3b (DNMT3b) were differentially expressed in chicken MD-resistant line 6 3 and MD-susceptible line 7 2 at 21 d after MDV infection. To better understand the role of methylation variation induced by MDV infection in both chicken lines, we mapped the genome-wide DNA methylation profiles in each line using Methyl-MAPS (methylation mapping analysis by paired-end sequencing). Collectively, the data sets collected in this study provide a more comprehensive picture of the chicken methylome. Overall, methylation levels were reduced in chickens from the resistant line 6 3 after MDV infection. We identified 11,512 infection-induced differential methylation regions (iDMRs). The number of iDMRs was larger in line 7 2 than in line 6 3, and most of iDMRs found in line 6 3 were overlapped with the iDMRs found in line 7 2. We further showed that in vitro methylation levels were associated with MDV replication, and found that MDV propagation in the infected cells was restricted by pharmacological inhibition of DNA methylation. Our results suggest that DNA methylation in the host may be associated with disease resistance or susceptibility. The methylation variations induced by viral infection may consequentially change the host transcriptome and result in diverse disease outcomes.

KEYWORDS:

DNA methylation; Marek’s disease; chicken; epigenetics; tumor; viral infection

PMID:
23538681
[PubMed - in process]
PMCID:
PMC3674052
Free PMC Article

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