Plasticity of DNA methylation in mouse T cell activation and differentiation

BMC Molecular Biology

Jun Y Fan⁴  M Frances Shannon¹  Chao Sun³  Stephen J Ohms²  Lina Ma⁴  Guobing Chen⁴  Yan Li⁴ 

[1] The University of Canberra, Canberra ACT 2602, Australia;ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia;College of Animal Science & Technology, Northwest A&F University, Yangling Shaanxi 712100, P. R. China;Department of Genome Biology, John Curtin School of Medical Research, The Australian National University, Canberra ACT 2601, Australia

关键词: Il2, Csf2;    T cell differentiation;    T cell activation;    DNA demethylation;   

Others  :  1091980
DOI  :  10.1186/1471-2199-13-16

 received in 2011-12-20, accepted in 2012-05-29,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Li et al; licensee BioMed Central Ltd.

【 图 表 】

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