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Plasticity of DNA methylation in mouse T cell activation and differentiation

Li, Yan; Chen, Guobing; Ma, Lina; Ohms, Stephen J; Sun, Chao; Shannon, M Frances; Fan, Jun Y

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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...[Show more]

dc.contributor.authorLi, Yan
dc.contributor.authorChen, Guobing
dc.contributor.authorMa, Lina
dc.contributor.authorOhms, Stephen J
dc.contributor.authorSun, Chao
dc.contributor.authorShannon, M Frances
dc.contributor.authorFan, Jun Y
dc.date.accessioned2015-12-23T00:53:19Z
dc.date.available2015-12-23T00:53:19Z
dc.identifier.issn1471-2199
dc.identifier.urihttp://hdl.handle.net/1885/95177
dc.description.abstractBACKGROUND 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.
dc.description.sponsorshipThis work was supported by an NHMRC project grant (ID 418048) and funded by an Epigenomics Capacity Development grant from Bioplatforms Australia to MFS. This research was also supported by a National Science Foundation of China Grant (No. 31172185) to CS. A scholarship from the Chinese Scholarship Council was awarded to YL.
dc.publisherBioMed Central
dc.rights© 2012 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.sourceBMC Molecular Biology
dc.subjectaging
dc.subjectanimals
dc.subjectcells, cultured
dc.subjectchromatin
dc.subjectgranulocyte-macrophage colony-stimulating factor
dc.subjectinterleukin-2
dc.subjectlymphocyte activation
dc.subjectmale
dc.subjectmice
dc.subjectmice, inbred c57bl
dc.subjectpromoter regions, genetic
dc.subjectt-lymphocytes, helper-inducer
dc.subjectcell differentiation
dc.subjectdna methylation
dc.titlePlasticity of DNA methylation in mouse T cell activation and differentiation
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume13
dc.date.issued2012-05-29
local.identifier.absfor060404
local.identifier.ariespublicationf5625xPUB978
local.publisher.urlhttp://www.biomedcentral.com/
local.type.statusPublished Version
local.contributor.affiliationLi, Yan, Northwest A&F University, China
local.contributor.affiliationChen, Guobing, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University
local.contributor.affiliationMa, Lina, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University
local.contributor.affiliationOhms, Stephen J, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, JCSMR General, The Australian National University
local.contributor.affiliationSun, Chao, Northwest A&F University, China
local.contributor.affiliationShannon, M Frances, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University
local.contributor.affiliationFan, Jun, College of Medicine, Biology and Environment, CMBE John Curtin School of Medical Research, Genome Sciences, The Australian National University
dc.relationhttp://purl.org/au-research/grants/nhmrc/418048
local.identifier.essn1471-2199
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage16
local.bibliographicCitation.lastpage19
local.identifier.doi10.1186/1471-2199-13-16
local.identifier.absseo920108
dc.date.updated2016-02-24T09:46:24Z
local.identifier.scopusID2-s2.0-84861473517
local.identifier.thomsonID000305832000001
CollectionsANU Research Publications

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