Plasticity of DNA methylation in mouse T cell activation and differentiation

Yan Li, Guobing Chen, Lina Ma, Stephen Ohms, Chao Sun, Frances Shannon, Jun Fan

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)1-19
Number of pages19
JournalBMC Molecular Biology
Volume13
DOIs
Publication statusPublished - 2012

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DNA Methylation
Cell Differentiation
T-Lymphocytes
Genome
Population
Methylation
T-Lymphocyte Subsets
Antigen-Presenting Cells
Helper-Inducer T-Lymphocytes
Plastics
Antigens
DNA
Enzymes
Genes

Cite this

Li, Yan ; Chen, Guobing ; Ma, Lina ; Ohms, Stephen ; Sun, Chao ; Shannon, Frances ; Fan, Jun. / Plasticity of DNA methylation in mouse T cell activation and differentiation. In: BMC Molecular Biology. 2012 ; Vol. 13. pp. 1-19.
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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 = "A demethylation, T cell activation, T cell differentiation, Il2, Csf2",
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Li, Y, Chen, G, Ma, L, Ohms, S, Sun, C, Shannon, F & Fan, J 2012, 'Plasticity of DNA methylation in mouse T cell activation and differentiation', BMC Molecular Biology, vol. 13, pp. 1-19. https://doi.org/10.1186/1471-2199-13-16

Plasticity of DNA methylation in mouse T cell activation and differentiation. / Li, Yan; Chen, Guobing; Ma, Lina; Ohms, Stephen; Sun, Chao; Shannon, Frances; Fan, Jun.

In: BMC Molecular Biology, Vol. 13, 2012, p. 1-19.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plasticity of DNA methylation in mouse T cell activation and differentiation

AU - Li, Yan

AU - Chen, Guobing

AU - Ma, Lina

AU - Ohms, Stephen

AU - Sun, Chao

AU - Shannon, Frances

AU - Fan, Jun

PY - 2012

Y1 - 2012

N2 - 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

AB - 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

KW - A demethylation

KW - T cell activation

KW - T cell differentiation

KW - Il2

KW - Csf2

U2 - 10.1186/1471-2199-13-16

DO - 10.1186/1471-2199-13-16

M3 - Article

VL - 13

SP - 1

EP - 19

JO - BMC Molecular Biology

JF - BMC Molecular Biology

SN - 1471-2199

ER -