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Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

Morikawa, Hiromasa and Ohkura, Naganari and Vandenbon, Alexis and Itoh, Masayoshi and Nagao-Sato, Sayaka and Kawaji, Hideya and Lassmann, Timo and Carninci, Piero and Hayashizaki, Yoshihide and Forrest, Alistair R. R. and Standley, Daron M. and Date, Hiroshi and Sakaguchi, Shimon and Fantom Consortium, . (2014) Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, H. 14. pp. 5289-5294.

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Official URL: http://edoc.unibas.ch/dok/A6254438

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Abstract

Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
UniBasel Contributors:van Nimwegen, Erik
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 May 2014 08:34
Deposited On:23 May 2014 08:34

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