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Logo of bmcmbBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Molecular Biology
 
BMC Mol Biol. 2012; 13: 16.
Published online May 29, 2012. doi:  10.1186/1471-2199-13-16
PMCID: PMC3386888
Plasticity of DNA methylation in mouse T cell activation and differentiation
Yan Li,1,2 Guobing Chen,2 Lina Ma,2 Stephen J Ohms,3 Chao Sun,corresponding author1 M Frances Shannon,corresponding author2,4 and Jun Y Fancorresponding author2
1College of Animal Science & Technology, Northwest A&F University, Yangling Shaanxi 712100, P. R. China
2Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia
3ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia
4The University of Canberra, Canberra ACT 2602, Australia
corresponding authorCorresponding author.
Yan Li: liyan790606/at/yahoo.com.cn; Guobing Chen: guobing.chen/at/nih.gov; Lina Ma: Lina.Ma/at/csiro.au; Stephen J Ohms: Stephen.Ohms/at/anu.edu.au; Chao Sun: sunchao2775/at/163.com; M Frances Shannon: frances.shannon/at/canberra.edu.au; Jun Y Fan: jun.fan/at/anu.edu.au
Received December 20, 2011; Accepted May 29, 2012.
Abstract
Background
Circulating CD4+ T helper cells are activated through interactions with antigen presenting cells and undergo differentiation into specific T helper cell subsets depending on the type of antigen encountered. In addition, the relative composition of the circulating CD4+ T cell population changes as animals mature with an increased percentage of the population being memory/effector type cells.
Results
Here, we report on the highly plastic nature of DNA methylation at the genome-wide level as T cells undergo activation, differentiation and aging. Of particular note were the findings that DNA demethylation occurred rapidly following T cell activation and that all differentiated T cell populations displayed lower levels of global methylation than the non-differentiated population. In addition, T cells from older mice had a reduced level of DNA methylation, most likely explained by the increase in the memory/effector cell fraction. Although significant genome-wide changes were observed, changes in DNA methylation at individual genes were restricted to specific cell types. Changes in the expression of enzymes involved in DNA methylation and demethylation reflect in most cases the changes observed in the genome-wide DNA methylation status.
Conclusion
We have demonstrated that DNA methylation is dynamic and flexible in CD4+ T cells and changes rapidly both in a genome-wide and in a targeted manner during T cell activation, differentiation. These changes are accompanied by parallel changes in the enzymatic complexes that have been implicated in DNA methylation and demethylation implying that the balance between these opposing activities may play a role in the maintaining the methylation profile of a given cell type but also allow flexibility in a cell population that needs to respond rapidly to environmental signals.
Keywords: DNA demethylation, T cell activation, T cell differentiation, Il2, Csf2
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